Endothelial dysfunction in metabolic diseases: Role of oxidation and possible therapeutic employment of N-acetylcysteine

Current Medicinal Chemistry

Volumn 21, Issue 32, 2014, Pages 3616-3635

  Masha, A ^a   Martina, V ^a  

^a UNIVERSITY OF TURIN   (Italy)

Author keywords

Antioxidants; cGMP; Diabetes mellitus; Metabolic syndrome; N acetylcysteine; Nitric oxide; Obesity; Oxidation; Oxidative stress; Polycystic ovary syndrome; Thiols

Indexed keywords

ACETYLCYSTEINE; ADVANCED GLYCATION END PRODUCT; ANGIOTENSIN II; ANTIOXIDANT; CYCLIC GMP; ENDOTHELIN 1; GLUTATHIONE; INSULIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 6; LUTEINIZING HORMONE; METFORMIN; MONOCYTE CHEMOTACTIC PROTEIN 1; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PLASMINOGEN ACTIVATOR INHIBITOR 1; PROTEIN KINASE C; THIOL; TUMOR NECROSIS FACTOR ALPHA; VASCULAR CELL ADHESION MOLECULE 1;

ADIPOCYTE; ANTIHYPERTENSIVE THERAPY; ANTIOXIDANT ACTIVITY; ARTICLE; BIOAVAILABILITY; BLOOD VESSEL REACTIVITY; BODY WEIGHT; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; DIABETES MELLITUS; DIABETIC PATIENT; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM CELL; ENZYME ACTIVITY; FAT MASS; GLUCOSE METABOLISM; HEART MUSCLE CELL; HUMAN; HYPERGLYCEMIA; HYPERINSULINEMIA; HYPERTENSION; INSULIN RESISTANCE; INSULIN SENSITIVITY; METABOLIC DISORDER; METABOLIC SYNDROME X; NONHUMAN; OBESITY; OVARY POLYCYSTIC DISEASE; OXIDATION; OXIDATIVE PHOSPHORYLATION; OXIDATIVE PHOSPHORYLATION UNCOUPLING; OXIDATIVE STRESS; PROTEIN GLYCOSYLATION; VASCULAR ENDOTHELIUM; VASODILATATION; ANIMAL; METABOLIC DISEASES; OXIDATION REDUCTION REACTION; PATHOPHYSIOLOGY;

ACETYLCYSTEINE; ANIMALS; ENDOTHELIUM, VASCULAR; HUMANS; METABOLIC DISEASES; OXIDATION-REDUCTION;

EID: 84929121142     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867321666140706132900     Document Type: Article

References (281)

1. Gimbrone, M. A. Jr. Vascular endothelium in hemostasis and thrombosis. Churchill Livingstone: Edimburgh, 1986.
2. Gimbrone, M. A. Jr; Bevilacqua, M. Vascular endothelium: functional modulation at the blood interface. In: Endothelial cell biology in health and disease; Simionescu, N.; Simionescu, M.; Plenum Press: New York 1988; pp. 255-273.
3. Vane, J. R.; Anggård, E. E.; Botting, R. M. Regulatory functions of the vascular endothelium. N. Engl. J. Med., 1990, 323, 27-36.
4. Collier, J.; Vallance, P. Endothelium-derived relaxing factor is an endogenous vasodilator in man. Br. J. Pharmacol., 1989, 97, 639-641.
5. Palmer, R. M.; Ferrige, A. G.; Moncada, S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature, 1987, 327, 524-526.
6. Ignarro, L. J.; Buga, G. M.; Wood, K. S.; Byrns, R. E.; Chaudhuri, G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc. Natl. Acad. Sci. U. S. A., 1987, 84, 9265-9269.
7. Furchgott, R. F.; Zawadzki, J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 1980, 288, 373-376.
8. Ignarro, L. J. Endothelium-derived nitric oxide: actions and properties. FASEB J., 1989, 3, 31-36.
9. Behrendt, D.; Ganz, P. Endothelial function. From vascular biology to clinical applications. Am. J. Cardiol., 2002, 90, 40L-48L.
10. Cayatte, A. J.; Palacino, J. J.; Horten, K.; Cohen, R. A. Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler. Thromb., 1994, 14, 753-759.
11. Ignarro, L. J. Nitric oxide: a unique endogenous signalling molecule in vascular biology. The Nobel Prize 1998 Medicine/Physiology Lecture, 1988, http://www.nobelprize.org/nobel-prizes/medicine/laureates/1998/ignarro-lecture.pdf.
12. Snyder, S. H. Nitric oxide: first in a new class of neurotransmitters. Science, 1992, 257, 494-496.
13. Vásquez-Vivar, J.; Kalyanaraman, B.; Martásek, P.; Hogg, N.; Masters, B. S.; Karoui, H.; Tordo, P.; Pritchard, K. A. Jr. Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc. Natl. Acad. Sci. USA, 1998, 95, 9220-9225.
14. Förstermann, U.; Boissel, J. P.; Kleinert, H. Expressional control of the 'constitutive' isoforms of nitric oxide synthase (NOS I and NOS III). FASEB J., 1998, 12, 773-790.
15. Li, H.; Brodsky, S.; Basco, M.; Romanov, V.; De Angelis, D. A.; Goligorsky, M. S. Nitric oxide attenuates signal transduction: possible role in dissociating caveolin-1 scaffold. Circ. Res., 2001, 88, 229-236.
16. Leiper, J.; Vallance, P. Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. Cardiovasc. Res., 1999, 43, 542-548.
17. Vallance, P. Importance of asymmetrical dimethylarginine in cardiovascular risk. Lancet, 2001, 358, 2096-2097.
18. Fujiwara, N.; Osanai, T.; Kamada, T.; Katoh, T.; Takahashi, K.; Okumura, K. Study on the relationship between plasma nitrite and nitrate level and salt sensitivity in human hypertension: modulation of nitric oxide synthesis by salt intake. Circulation, 2000, 101, 856-861.
19. Singh, R. J.; Hogg, N.; Joseph, J.; Kalyanaraman, B. Mechanism of nitric oxide release from S-nitrosothiols. J. Biol. Chem., 1996, 271, 18596-18603.
20. Stubauer, G.; Giuffrè, A.; Sarti, P. Mechanism of S-nitrosothiol formation and degradation mediated by copper ions. J. Biol. Chem., 1999, 274, 28128-28133.
21. Hogg, N. The biochemistry and physiology of S-nitrosothiols. Annu. Rev. Pharmacol. Toxicol., 2002, 42, 585-600.
22. Feelisch, M.; Stamler, J. S. Preparation and detection of Snitrosothiols. In: Methods in Nitric Oxide Research. West Sussex, UK: John Wiley & Sons Inc. 1996, 36, 521-539.
23. Zhang, Y.; Hogg, N. The mechanism of transmembrane Snitrosothiol transport. Proc. Natl. Acad. Sci. USA., 2004, 101, 7891-7896.
24. Lohmann, S. M.; Vaandrager, A. B.; Smolenski, A.; Walter, U.; De Jonge, H. R. Distinct and specific functions of cGMP-dependent protein kinases. Trends. Biochem. Sci., 1997, 22, 307-312.
25. Münzel, T.; Feil, R.; Mülsch, A.; Lohmann, S. M.; Hofmann, F.; Walter, U. Physiology and pathophysiology of vascular signaling controlled by guanosine 3', 5'-cyclic monophosphate-dependent protein kinase. Circulation, 2003, 108, 2172-2183.
26. Jia, L.; Bonaventura, C.; Bonaventura, J.; Stamler, J. S. Snitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature, 1996, 380, 221-226.
27. Spiecker, M.; Peng, H. B.; Liao, J. K. Inhibition of endothelial vascular cell adhesion molecule-1 expression by nitric oxide involves the induction and nuclear translocation of IkappaBalpha. J. Biol. Chem., 1997, 272, 30969-30974.
28. Sekkaï, D.; Aillet, F.; Israël, N.; Lepoivre, M. Inhibition of NFkappaB and HIV-1 long terminal repeat transcriptional activation by inducible nitric oxide synthase 2 activity. J. Biol. Chem., 1998, 273, 3895-3900.
29. Lander, H. M.; Ogiste, J. S.; Pearce, S. F.; Levi, R.; Novogrodsky, A. Nitric oxide-stimulated guanine nucleotide exchange on p21ras. J. Biol. Chem., 1995, 270, 7017-7020.
30. Lander, H. M.; Hajjar, D. P.; Hempstead, B. L.; Mirza, U. A.; Chait, B. T.; Campbell, S.; Quilliam, L. A. A molecular redox switch on p21 (ras). Structural basis for the nitric oxide-p21 (ras) interaction. J. Biol. Chem., 1997, 272, 4323-4326.
31. Ignarro, L. J. Plenary lecture. Proceedings of the "1st International meeting on nitric oxide. From basic science to clinical evidence". Barcelona, Spain, 2003.
32. Gokce, N.; Keaney, J. F. Jr.; Vita, J. A. Endotheliopathies: clinical manifestations of endothelial dysfunction. In: Thrombosis and hemorrhage; Loscalzo, J.; Shafer, A. I. 2nd Ed. Baltimore: Williams and Wilkins 1998, 901-924.
33. Gimbrone, M. A. Jr.; Kume, N.; Cybulsky, M. I. Vascular endothelial dysfunction and the pathogenesis of atherosclerosis. In: Atherosclerosis Reviews, vol 25; Weber, P.; Leaf, A. New York: Raven Press, 1993, 1-9.
34. Vita, J. A.; Treasure, C. B.; Nabel, E. G.; McLenachan, J. M.; Fish, R. D.; Yeung, A. C.; Vekshtein, V. I.; Selwyn, A. P.; Ganz, P. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation, 1990, 81, 491-497.
35. Schächinger, V.; Britten, M. B.; Zeiher, A. M. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation, 2000, 101, 1899-1906.
36. Heitzer, T.; Schlinzig, T.; Krohn, K.; Meinertz, T.; Münzel, T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation, 2001, 104, 2673-2678.
37. Srivastava, K.; Narang, R.; Sreenivas, V.; Das, S.; Das, N. Association of eNOS Glu298Asp gene polymorphism with essential hypertension in Asian Indians. Clin. Chim. Acta, 2008, 387, 80-83.
38. Antoniades, C.; Tousoulis, D.; Vasiliadou, C.; Pitsavos, C.; Toutouza, M.; Tentolouris, C.; Marinou, K.; Stefanadis, C. Genetic polymorphisms G894T on the eNOS gene is associated with endothelial function and vWF levels in premature myocardial infarction survivors. Int. J. Cardiol., 2006, 107, 95-100.
39. De Gennaro Colonna, V.; Bianchi, M.; Pascale, V.; Ferrario, P.; Morelli, F.; Pascale, W.; Tomasoni, L.; Turiel, M. Asymmetric dimethylarginine (ADMA): an endogenous inhibitor of nitric oxide synthase and a novel cardiovascular risk molecule. Med. Sci. Monit., 2009, 15, RA91-RA101.
40. Crabtree, M. J.; Smith, C. L.; Lam, G.; Goligorsky, M. S.; Gross, S. S. Ratio of 5, 6, 7, 8-tetrahydrobiopterin to 7, 8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS. Am. J. Physiol. Heart. Circ. Physiol., 2008, 294, H1530-H1540.
41. Mingone, C. J.; Gupte, S. A.; Ali, N.; Oeckler, R. A.; Wolin, M. S. Thiol oxidation inhibits nitric oxide-mediated pulmonary artery relaxation and guanylate cyclase stimulation. Am. J. Physiol. Lung. Cell. Mol. Physiol., 2006, 290, L549-L557.
42. Beckman, J. S. Oxidative damage and tyrosine nitration from peroxynitrite. Chem. Res. Toxicol., 1996, 9, 836-844.
43. Stasch, J. P.; Schmidt, P. M.; Nedvetsky, P. I.; Nedvetskaya, T. Y.; HS, A. K.; Meurer, S.; Deile, M.; Taye, A.; Knorr, A.; Lapp, H.; Müller, H.; Turgay, Y.; Rothkegel, C.; Tersteegen, A.; Kemp-Harper, B.; Müller-Esterl, W.; Schmidt, H. H. Targeting the hemeoxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J. Clin. Invest., 2006, 116, 2552-2561.
44. Channon, K. M.; Qian, H.; George, S. E. Nitric oxide synthase in atherosclerosis and vascular injury: insights from experimental gene therapy. Arterioscler. Thromb. Vasc. Biol., 2000, 20, 1873-1881.
45. Ackworth, I. N.; Bailey, B. The Handbook of oxidative metabolism. 1995.
46. Schulz, E.; Jansen, T.; Wenzel, P.; Daiber, A.; Münzel, T. Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension. Antioxid. Redox. Signal., 2008, 10, 1115-1126.
47. Mollnau, H.; Wendt, M.; Szöcs, K.; Lassègue, B.; Schulz, E.; Oelze, M.; Li, H.; Bodenschatz, M.; August, M.; Kleschyov, A. L.; Tsilimingas, N.; Walter, U.; Förstermann, U.; Meinertz, T.; Griendling, K.; Münzel, T. Effects of angiotensin II infusion on the expression and function of NAD (P) H oxidase and components of nitric oxide/cGMP signaling. Circ. Res., 2002, 90, E58-E65.
48. Stamler, J.; Vaccaro, O.; Neaton, J. D.; Wentworth, D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care, 1993, 16, 434-444.
49. Honing, M. L.; Morrison, P. J.; Banga, J. D.; Stroes, E. S.; Rabelink, T. J. Nitric oxide availability in diabetes mellitus. Diabetes Metab. Rev., 1998, 14, 241-249.
50. Veves, A.; Akbari, C. M.; Primavera, J.; Donaghue, V. M.; Zacharoulis, D.; Chrzan, J. S.; De Girolami, U.; Lo Gerfo, F. W.; Freeman, R. Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration. Diabetes, 1998, 47, 457-463.
51. Bohlen, H. G.; Lash, J. M. Topical hyperglycemia rapidly suppresses EDRF-mediated vasodilation of normal rat arterioles. Am. J. Physiol., 1993, 265, H219-H225.
52. De Vriese, A. S.; Verbeuren, T. J.; Van De Voorde, J.; Lameire, N. H.; Vanhoutte, P. M. Endothelial dysfunction in diabetes. Br. J. Pharmacol., 2000, 130, 963-974.
53. Kobayashi, T.; Kamata, K. Relationship among cholesterol, superoxide anion and endothelium-dependent relaxation in diabetic rats. Eur. J. Pharmacol., 1999, 367, 213-222.
54. Rodríguez-Mañas, L.; Angulo, J.; Peiró, C.; Llergo, J. L.; Sánchez-Ferrer, A.; López-Dóriga, P.; Sánchez-Ferrer, C. F. Endothelial dysfunction and metabolic control in streptozotocin-induced diabetic rats. Br. J. Pharmacol., 1998, 123, 1495-1502.
55. Giugliano, D.; Marfella, R.; Coppola, L.; Verrazzo, G.; Acampora, R.; Giunta, R.; Nappo, F.; Lucarelli, C.; D'Onofrio, F. Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia. Circulation, 1997, 95, 1783-1790.
56. Johnstone, M. T.; Creager, S. J.; Scales, K. M.; Cusco, J. A.; Lee, B. K.; Creager, M. A. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation, 1993, 88, 2510-2516.
57. Williams, S. B.; Cusco, J. A.; Roddy, M. A.; Johnstone, M. T.; Creager, M. A. Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus. J. Am. Coll. Cardiol., 1996, 27, 567-574.
58. Balletshofer, B. M.; Rittig, K.; Enderle, M. D.; Volk, A.; Maerker, E.; Jacob, S.; Matthaei, S.; Rett, K.; Häring, H. U. Endothelial dysfunction is detectable in young normotensive first-degree relatives of subjects with type 2 diabetes in association with insulin resistance. Circulation, 2000, 101, 1780-1784.
59. Tesauro, M.; Rizza, S.; Iantorno, M.; Campia, U.; Cardillo, C.; Lauro, D.; Leo, R.; Turriziani, M.; Cocciolillo, G. C.; Fusco, A.; Panza, J. A.; Scuteri, A.; Federici, M.; Lauro, R.; Quon, M. J. Vascular, metabolic, and inflammatory abnormalities in normoglycemic offspring of patients with type 2 diabetes mellitus. Metabolism, 2007, 56, 413-419.
60. Hartell, N. A.; Archer, H. E.; Bailey, C. J. Insulin-stimulated endothelial nitric oxide release is calcium independent and mediated via protein kinase B. Biochem. Pharmacol., 2005, 69, 781-790.
61. Duncan, E. R.; Crossey, P. A.; Walker, S.; Anilkumar, N.; Poston, L.; Douglas, G.; Ezzat, V. A.; Wheatcroft, S. B.; Shah, A. M.; Kearney, M. T. Effect of endothelium-specific insulin resistance on endothelial function in vivo. Diabetes, 2008, 57, 3307-3314.
62. Wheatcroft, S. B.; Williams, I. L.; Shah, A. M.; Kearney, M. T. Pathophysiological implications of insulin resistance on vascular endothelial function. Diabetes Med., 2003, 20, 255-268.
63. Montagnani, M.; Golovchenko, I.; Kim, I.; Koh, G. Y.; Goalstone, M. L.; Mundhekar, A. N.; Johansen, M.; Kucik, D. F.; Quon, M. J.; Draznin, B. Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. J. Biol. Chem., 2002, 277, 1794-1799.
64. Mather, K. J.; Verma, S.; Anderson, T. J. Improved endothelial function with metformin in type 2 diabetes mellitus. J. Am. Coll. Cardiol., 2001, 37, 1344-1350.
65. Pistrosch, F.; Passauer, J.; Fischer, S.; Fuecker, K.; Hanefeld, M.; Gross, P. In type 2 diabetes, rosiglitazone therapy for insulin resistance ameliorates endothelial dysfunction independent of glucose control. Diabetes Care, 2004, 27, 484-490.
66. Mehta, J. L.; Rasouli, N.; Sinha, A. K.; Molavi, B. Oxidative stress in diabetes: a mechanistic overview of its effects on atherogenesis and myocardial dysfunction. Int. J. Biochem. Cell. Biol., 2006, 38, 794-803.
67. Vincent, A. M.; Russell, J. W.; Low, P.; Feldman, E. L. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr. Rev., 2004, 25, 612-628.
68. Turko, I. V.; Marcondes, S.; Murad, F. Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoA:3-oxoacid CoAtransferase. Am. J. Physiol. Heart. Circ. Physiol., 2001, 281, H2289-H2294.
69. Nishikawa, T.; Edelstein, D.; Du, X. L.; Yamagishi, S.; Matsumura, T.; Kaneda, Y.; Yorek, M. A.; Beebe, D.; Oates, P. J.; Hammes, H. P.; Giardino, I.; Brownlee, M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature, 2000, 404, 787-790.
70. Brownlee, M. Biochemistry and molecular cell biology of diabetic complications. Nature, 2001, 414, 813-820.
71. Bitar, M. S.; Wahid, S.; Mustafa, S.; Al-Saleh, E.; Dhaunsi, G. S.; Al-Mulla, F. Nitric oxide dynamics and endothelial dysfunction in type II model of genetic diabetes. Eur. J. Pharmacol., 2005, 511, 53-64.
72. Chew, G. T.; Watts, G. F. Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the 'recoupling hypothesis'. QJM, 2004, 97, 537-548.
73. Vlassara, H.; Palace, M. R. Diabetes and advanced glycation endproducts. J. Intern. Med., 2002, 251, 87-101.
74. Chung, S. S.; Ho, E. C.; Lam, K. S.; Chung, S. K. Contribution of polyol pathway to diabetes-induced oxidative stress. J. Am. Soc. Nephrol., 2003, 14, S233-S236.
75. Ishii, H.; Koya, D.; King, G. L. Protein kinase C activation and its role in the development of vascular complications in diabetes mellitus. J. Mol. Med. (Berl.), 1998, 76, 21-31.
76. Wascher, T. C. Reducing oxidative stress in diabetes: experimental evidence and potential clinical implications. In: Vascular disease in diabetes; Tooke, J. Tunbridge Wells: Wells Healthcare Communications Limited, 2001, 107-130.
77. Johansen, J. S.; Harris, A. K.; Rychly, D. J.; Ergul, A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc. Diabetol., 2005, 4, 5.
78. Tesfamariam, B.; Brown, M. L.; Cohen, R. A. Elevated glucose impairs endothelium-dependent relaxation by activating protein kinase C. J. Clin. Invest., 1991, 87, 1643-1648.
79. Zieman, S.; Kass, D. Advanced glycation end product crosslinking: pathophysiologic role and therapeutic target in cardiovascular disease. Congest. Heart. Fail., 2004, 10, 144-149.
80. Odetti, P.; Cosso, L.; Pronzato, M. A.; Dapino, D.; Gurreri, G. Plasma advanced glycosylation end-products in maintenance haemodialysis patients. Nephrol. Dial. Transplant., 1995, 10, 2110-2113.
81. Thorpe, S. R.; Baynes, J. W. Role of the Maillard reaction in diabetes mellitus and diseases of aging. Drugs Aging., 1996, 9, 69-77.
82. Basta, G.; Lazzerini, G.; Massaro, M.; Simoncini, T.; Tanganelli, P.; Fu, C.; Kislinger, T.; Stern, D. M.; Schmidt, A. M.; De Caterina, R. Advanced glycation end products activate endothelium through signal-transduction receptor RAGE: a mechanism for amplification of inflammatory responses. Circulation, 2002, 105, 816-822.
83. Wautier, M. P.; Chappey, O.; Corda, S.; Stern, D. M.; Schmidt, A. M.; Wautier, J. L. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am. J. Physiol. Endocrinol. Metab., 2001, 280, E685-E694.
84. Fiuza, C.; Bustin, M.; Talwar, S.; Tropea, M.; Gerstenberger, E.; Shelhamer, J. H.; Suffredini, A. F. Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells. Blood, 2003, 101:2652-2660.
85. Xu, J.; Xie, J.; Bao, M.; Li, Z.; Yang, Z. NF-kappaB/I-kappaB pathway during ischemia reperfusion injury of rat liver. Chin. Med. J. (Engl)., 2003, 116, 1146-1149.
86. Tsilibary, E. C.; Kitsiou, P. V.; Phenekos, C. V.; Frangoulopoulos, E. Glucose induced changes of cell shape and integrin expression in murine, insulin-secreting pancreatic β-cells. IDF/EASD, August 25-28, Paris, FR;Diabetologia, abst., Volume 2003.
87. Zhou, Z.; Wang, K.; Penn, M. S.; Marso, S. P.; Lauer, M. A.; Forudi, F.; Zhou, X.; Qu, W.; Lu, Y.; Stern, D. M.; Schmidt, A. M.; Lincoff, A. M.; Topol, E. J. Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury. Circulation, 2003, 107, 2238-2243.
88. Du, X. L.; Edelstein, D.; Rossetti, L.; Fantus, I. G.; Goldberg, H.; Ziyadeh, F.; Wu, J.; Brownlee, M. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc. Natl. Acad. Sci. USA, 2000, 97, 12222-12226.
89. Ting, H. H.; Timimi, F. K.; Boles, K. S.; Creager, S. J.; Ganz, P.; Creager, M. A. Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J. Clin. Invest., 1996, 97, 22-28.
90. Blough, N. V.; Zafiriou, O. C. Reaction of superoxide with nitric oxide to form peroxonitrite in alkaline aqueous solution. Inorg. Chem., 1985, 24, 3504-3505.
91. Evgenov, O. V.; Pacher, P.; Schmidt, P. M.; Haskó, G.; Schmidt, H. H.; Stasch, J. P. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat. Rev. Drug. Discov., 2006, 5, 755-768.
92. Ritchie, S. A.; Connell, J. M. The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutr. Metab. Cardiovasc. Dis., 2007, 17, 319-326.
93. Pascual, M.; Pascual, D. A.; Soria, F.; Vicente, T.; Hernández, A. M.; Tébar, F. J.; Valdés, M. Effects of isolated obesity on systolic and diastolic left ventricular function. Heart, 2003, 89, 1152-1156.
94. Alpert, M. A. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am. J. Med. Sci., 2001, 321, 225-236.
95. Bohlen, H. G. Mechanisms for early microvascular injury in obesity and type II diabetes. Curr. Hypertens. Rep., 2004, 6, 60-65.
96. Steinberg, H. O.; Chaker, H.; Leaming, R.; Johnson, A.; Brechtel, G.; Baron, A. D. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J. Clin. Invest., 1996, 97, 2601-2610.
97. Bigornia, S. J.; Mott, M. M.; Hess, D. T.; Apovian, C. M.; McDonnell, M. E.; Duess, M. A.; Kluge, M. A.; Fiscale, A. J.; Vita, J. A.; Gokce, N. Long-term successful weight loss improves vascular endothelial function in severely obese individuals. Obesity (Silver Spring)., 2010, 18, 754-759.
98. Woo, K. S.; Chook, P.; Yu, C. W.; Sung, R. Y.; Qiao, M.; Leung, S. S.; Lam, C. W.; Metreweli, C.; Celermajer, D. S. Overweight in children is associated with arterial endothelial dysfunction and intimamedia thickening. Int. J. Obes. Relat. Metab. Disord., 2004, 28, 852-857.
99. Bohlen, H. G.; Nase, G. P. Obesity lowers hyperglycemic threshold for impaired in vivo endothelial nitric oxide function. Am. J. Physiol. Heart. Circ. Physiol., 2002, 283, H391-H397.
100. Frisbee, J. C.; Stepp, D. W. Impaired NO-dependent dilation of skeletal muscle arterioles in hypertensive diabetic obese Zucker rats. Am. J. Physiol. Heart. Circ. Physiol., 2001, 281, H1304-H1311.
101. Fujiwara, K.; Hayashi, K.; Matsuda, H.; Kubota, E.; Honda, M.; Ozawa, Y.; Saruta, T. Altered pressure-natriuresis in obese Zucker rats. Hypertension, 1999, 33, 1470-1475.
102. Karagiannis, J.; Reid, J. J.; Darby, I.; Roche, P.; Rand, M. J.; Li, C. G. Impaired nitric oxide function in the basilar artery of the obese Zucker rat. J. Cardiovasc. Pharmacol., 2003, 42, 497-505.
103. Martin, J. W.; Briesmiester, K.; Bargardi, A.; Muzik, O.; Mosca, L.; Duvernoy, C. S. Weight changes and obesity predict impaired resting and endothelium-dependent myocardial blood flow in postmenopausal women. Clin. Cardiol., 2005, 28, 13-18.
104. Prakash, R.; Mintz, J. D.; Stepp, D. W. Impact of obesity on coronary microvascular function in the Zucker rat. Microcirculation, 2006, 13, 389-396.
105. Tesauro, M.; Schinzari, F.; Iantorno, M.; Rizza, S.; Melina, D.; Lauro, D.; Cardillo, C. Ghrelin improves endothelial function in patients with metabolic syndrome. Circulation, 2005, 112, 2986-2992.
106. Ferri, C.; Bellini, C.; Desideri, G.; Baldoncini, R.; Properzi, G.; Santucci, A.; De Mattia, G. Circulating endothelin-1 levels in obese patients with the metabolic syndrome. Exp. Clin. Endocrinol. Diabetes., 1997, 105 Suppl 2, 38-40.
107. Piatti, P. M.; Monti, L. D.; Galli, L.; Fragasso, G.; Valsecchi, G.; Conti, M.; Gernone, F.; Pontiroli, A. E. Relationship between endothelin-1 concentration and metabolic alterations typical of the insulin resistance syndrome. Metabolism, 2000, 49, 748-752.
108. Mather, K. J.; Lteif, A.; Steinberg, H. O.; Baron, A. D. Interactions between endothelin and nitric oxide in the regulation of vascular tone in obesity and diabetes. Diabetes, 2004, 53, 2060-2066.
109. Cardillo, C.; Campia, U.; Iantorno, M.; Panza, J. A. Enhanced vascular activity of endogenous endothelin-1 in obese hypertensive patients. Hypertension, 2004, 43, 36-40.
110. Wellen, K. E.; Hotamisligil, G. S. Obesity-induced inflammatory changes in adipose tissue. J. Clin. Invest., 2003, 112, 1785-1788.
111. Ziccardi, P.; Nappo, F.; Giugliano, G.; Esposito, K.; Marfella, R.; Cioffi, M.; D'Andrea, F.; Molinari, A. M.; Giugliano, D. Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation, 2002, 105, 804-809.
112. Yoshizumi, M.; Perrella, M. A.; Burnett, J. C. Jr.; Lee, M. E. Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life. Circ. Res., 1993, 73, 205-209.
113. Mohamed, F.; Monge, J. C.; Gordon, A.; Cernacek, P.; Blais, D.; Stewart, D. J. Lack of role for nitric oxide (NO) in the selective destabilization of endothelial NO synthase mRNA by tumor necrosis factor-alpha. Arterioscler. Thromb. Vasc. Biol., 1995, 15, 52-57.
114. De Keulenaer, G. W.; Alexander, R. W.; Ushio-Fukai, M.; Ishizaka, N.; Griendling, K. K Tumour necrosis factor alpha activates a p22phox-based NADH oxidase in vascular smooth muscle. Biochem. J., 1998, 329, 653-657.
115. Tesauro, M.; Schinzari, F.; Rovella, V.; Melina, D.; Mores, N.; Barini, A.; Mettimano, M.; Lauro, D.; Iantorno, M.; Quon, M. J.; Cardillo, C. Tumor necrosis factor-alpha antagonism improves vasodilation during hyperinsulinemia in metabolic syndrome. Diabetes Care, 2008, 31, 1439-1441.
116. Martin, S. S.; Qasim, A.; Reilly, M. P. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J. Am. Coll. Cardiol., 2008, 52, 1201-1210.
117. Sweeney, G. Cardiovascular effects of leptin. Nat. Rev. Cardiol., 2010, 7, 22-29.
118. Söderberg, S.; Ahrén, B.; Jansson, J. H.; Johnson, O.; Hallmans, G.; Asplund, K.; Olsson, T. Leptin is associated with increased risk of myocardial infarction. J. Intern. Med., 1999, 246, 409-418.
119. Söderberg, S.; Stegmayr, B.; Ahlbeck-Glader, C.; Slunga-Birgander, L.; Ahrén, B.; Olsson, T. High leptin levels are associated with stroke. Cerebrovasc. Dis., 2003, 15, 63-69.
120. Wallace, A. M.; McMahon, A. D.; Packard, C. J.; Kelly, A.; Shepherd, J.; Gaw, A.; Sattar, N. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation, 2001, 104, 3052-3056.
121. Yamauchi, T.; Kamon, J.; Minokoshi, Y.; Ito, Y.; Waki, H.; Uchida, S.; Yamashita, S.; Noda, M.; Kita, S.; Ueki, K.; Eto, K.; Akanuma, Y.; Froguel, P.; Foufelle, F.; Ferre, P.; Carling, D.; Kimura, S.; Nagai, R.; Kahn, B. B.; Kadowaki, T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med., 2002, 8, 1288-1295.
122. Frühbeck, G. A heliocentric view of leptin. Proc. Nutr. Soc., 2001, 60, 301-318.
123. Schäfer, K.; Halle, M.; Goeschen, C.; Dellas, C.; Pynn, M.; Loskutoff, D. J.; Konstantinides, S. Leptin promotes vascular remodeling and neointimal growth in mice. Arterioscler. Thromb. Vasc. Biol., 2004, 24, 112-117.
124. Söderberg, S.; Olsson, T.; Eliasson, M.; Johnson, O.; Ahrén, B. Plasma leptin levels are associated with abnormal fibrinolysis in men and postmenopausal women. J. Intern. Med., 1999, 245, 533-543.
125. Korda, M.; Kubant, R.; Patton, S.; Malinski, T. Leptin-induced endothelial dysfunction in obesity. Am. J. Physiol. Heart. Circ. Physiol., 2008, 295, H1514-H1521.
126. Yamagishi, S. I.; Edelstein, D.; Du, X. L.; Kaneda, Y.; Guzmán, M.; Brownlee, M. Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J. Biol. Chem., 2001, 276, 25096-25100.
127. Beltowski, J.; Wójcicka, G.; Jamroz, A. Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia. Atherosclerosis, 2003, 170, 21-29.
128. Cleland, S. J.; Sattar, N.; Petrie, J. R.; Forouhi, N. G.; Elliott, H. L.; Connell, J. M. Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clin. Sci. (Lond)., 2000, 98, 531-535.
129. Kazumi, T.; Kawaguchi, A.; Hirano, T.; Yoshino, G. C-reactive protein in young, apparently healthy men: associations with serum leptin, QTc interval, and high-density lipoprotein-cholesterol. Metabolism, 2003, 52, 1113-1116.
130. Matsubara, M.; Maruoka, S.; Katayose, S. Inverse relationship between plasma adiponectin and leptin concentrations in normalweight and obese women. Eur. J. Endocrinol., 2002, 147, 173-180.
131. Ouchi, N.; Kihara, S.; Arita, Y.; Maeda, K.; Kuriyama, H.; Okamoto, Y.; Hotta, K.; Nishida, M.; Takahashi, M.; Nakamura, T.; Yamashita, S.; Funahashi, T.; Matsuzawa, Y. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation, 1999, 100, 2473-2476.
132. Hotta, K.; Funahashi, T.; Bodkin, N. L.; Ortmeyer, H. K.; Arita, Y.; Hansen, B. C.; Matsuzawa, Y. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes., 2001, 50, 1126-1133.
133. Shimabukuro, M.; Higa, N.; Asahi, T.; Oshiro, Y.; Takasu, N.; Tagawa, T.; Ueda, S.; Shimomura, I.; Funahashi, T.; Matsuzawa, Y. Hypoadiponectinemia is closely linked to endothelial dysfunction in man. J. Clin. Endocrinol. Metab., 2003, 88, 3236-3240.
134. Chen, H.; Montagnani, M.; Funahashi, T.; Shimomura, I.; Quon, M. J. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J. Biol. Chem., 2003, 278, 45021-45026.
135. Eid, H. M.; Lyberg, T.; Arnesen, H.; Seljeflot, I. Insulin and adiponectin inhibit the TNFalpha-induced ADMA accumulation in human endothelial cells: the role of DDAH. Atherosclerosis, 2007, 194, E1-E8.
136. Motoshima, H.; Wu, X.; Mahadev, K.; Goldstein, B. J. Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem. Biophys. Res. Commun., 2004, 315, 264-271.
137. Yokota, T.; Oritani, K.; Takahashi, I.; Ishikawa, J.; Matsuyama, A.; Ouchi, N.; Kihara, S.; Funahashi, T.; Tenner, A. J.; Tomiyama, Y.; Matsuzawa, Y. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood, 2000, 96, 1723-1732.
138. Ouchi, N.; Kihara, S.; Arita, Y.; Okamoto, Y.; Maeda, K.; Kuriyama, H.; Hotta, K.; Nishida, M.; Takahashi, M.; Muraguchi, M.; Ohmoto, Y.; Nakamura, T.; Yamashita, S.; Funahashi, T.; Matsuzawa, Y. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation, 2000, 102, 1296-1301.
139. Beltowski, J. Adiponectin and resistin-new hormones of white adipose tissue. Med. Sci. Monit., 2003, 9, RA55-RA61.
140. Verma, S.; Li, S. H.; Wang, C. H.; Fedak, P. W.; Li, R. K.; Weisel, R. D.; Mickle, D. A. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation, 2003, 108, 736-740.
141. Kawanami, D.; Maemura, K.; Takeda, N.; Harada, T.; Nojiri, T.; Imai, Y.; Manabe, I.; Utsunomiya, K.; Nagai, R. Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem. Biophys. Res. Commun., 2004, 314, 415-419.
142. Tschöp, M.; Weyer, C.; Tataranni, P. A.; Devanarayan, V.; Ravussin, E.; Heiman, M. L. Circulating ghrelin levels are decreased in human obesity. Diabetes, 2001, 50, 707-709.
143. Tesauro, M.; Schinzari, F.; Rovella, V.; Di Daniele, N.; Lauro, D.; Mores, N.; Veneziani, A.; Cardillo, C. Ghrelin restores the endothelin 1/nitric oxide balance in patients with obesity-related metabolic syndrome. Hypertension, 2009, 54, 995-1000.
144. Iantorno, M.; Chen, H.; Kim, J. A.; Tesauro, M.; Lauro, D.; Cardillo, C.; Quon, M. J. Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells. Am. J. Physiol. Endocrinol. Metab., 2007, 292, E756-E764.
145. Davda, R. K.; Stepniakowski, K. T.; Lu, G.; Ullian, M. E.; Goodfriend, T. L.; Egan, B. M. Oleic acid inhibits endothelial nitric oxide synthase by a protein kinase C-independent mechanism. Hypertension., 1995, 26, 764-770.
146. Watanabe, S.; Tagawa, T.; Yamakawa, K.; Shimabukuro, M.; Ueda, S. Inhibition of the renin-angiotensin system prevents free fatty acid-induced acute endothelial dysfunction in humans. Arterioscler. Thromb. Vasc. Biol., 2005, 25, 2376-2380.
147. Piatti, P. M.; Monti, L. D.; Conti, M.; Baruffaldi, L.; Galli, L.; Phan, C. V.; Guazzini, B.; Pontiroli, A. E.; Pozza, G. Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in humans. Diabetes, 1996, 45, 316-321.
148. Dresner, A.; Laurent, D.; Marcucci, M.; Griffin, M. E.; Dufour, S.; Cline, G. W.; Slezak, L. A.; Andersen, D. K.; Hundal, R. S.; Rothman, D. L.; Petersen, K. F.; Shulman, G. I. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J. Clin. Invest., 1999, 103, 253-259.
149. Lu, G.; Greene, E. L.; Nagai, T.; Egan, B. M. Reactive oxygen species are critical in the oleic acid-mediated mitogenic signaling pathway in vascular smooth muscle cells. Hypertension, 1998, 32, 1003-1010.
150. Grundy, S. M. Metabolic syndrome: a multiplex cardiovascular risk factor. J. Clin. Endocrinol. Metab., 2007, 92, 399-404.
151. Suzuki, T.; Hirata, K.; Elkind, M. S.; Jin, Z.; Rundek, T.; Miyake, Y.; Boden-Albala, B.; Di Tullio, M. R.; Sacco, R.; Homma, S. Metabolic syndrome, endothelial dysfunction, and risk of cardiovascular events: the Northern Manhattan Study (NOMAS). Am. Heart. J., 2008, 156, 405-410.
152. Benjamin, E. J.; Larson, M. G.; Keyes, M. J.; Mitchell, G. F.; Vasan, R. S.; Keaney, J. F. Jr.; Lehman, B. T.; Fan, S.; Osypiuk, E.; Vita, J. A. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation, 2004, 109, 613-619.
153. Kuvin, J. T.; Patel, A. R.; Sidhu, M.; Rand, W. M.; Sliney, K. A.; Pandian, N. G.; Karas, R. H. Relation between high-density lipoprotein cholesterol and peripheral vasomotor function. Am. J. Cardiol., 2003, 92, 275-279.
154. Girman, C. J.; Rhodes, T.; Mercuri, M.; Pyörälä, K.; Kjekshus, J.; Pedersen, T. R.; Beere, P. A.; Gotto, A. M.; Clearfield, M.; 4S Group and the AFCAPS/TexCAPS Research Group. The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Am. J. Cardiol., 2004, 93, 136-141.
155. Meigs, J. B.; Hu, F. B.; Rifai, N.; Manson, J. E. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA, 2004, 291, 1978-1786.
156. De Jongh, R. T.; Serné, E. H.; IJzerman, R. G.; De Vries, G.; Stehouwer, C. D. Impaired microvascular function in obesity: implications for obesity-associated microangiopathy, hypertension, and insulin resistance. Circulation, 2004, 109, 2529-2535.
157. Esposito, K.; Ciotola, M.; Carleo, D.; Schisano, B.; Saccomanno, F.; Sasso, F. C.; Cozzolino, D.; Assaloni, R.; Merante, D.; Ceriello, A.; Giugliano, D. Effect of rosiglitazone on endothelial function and inflammatory markers in patients with the metabolic syndrome. Diabetes Care, 2006, 29, 1071-1076.
158. Hamburg, N. M.; Larson, M. G.; Vita, J. A.; Vasan, R. S.; Keyes, M. J.; Widlansky, M. E.; Fox, C. S.; Mitchell, G. F.; Levy, D.; Meigs, J. B.; Benjamin, E. J. Metabolic syndrome, insulin resistance, and brachial artery vasodilator function in Framingham Offspring participants without clinical evidence of cardiovascular disease. Am. J. Cardiol., 2008, 101, 82-88.
159. Wellen, K. E.; Hotamisligil, G. S. Inflammation, stress, and diabetes. J. Clin. Invest., 2005, 115, 1111-1119.
160. Festa, A.; D'Agostino, R. Jr.; Howard, G.; Mykkänen, L.; Tracy, R. P.; Haffner, S. M. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation, 2000, 102, 42-47.
161. Stocker, R.; Keaney, J. F. Jr. Role of oxidative modifications in atherosclerosis. Physiol. Rev., 2004, 84, 1381-1478.
162. Furukawa, S.; Fujita, T.; Shimabukuro, M.; Iwaki, M.; Yamada, Y.; Nakajima, Y.; Nakayama, O.; Makishima, M.; Matsuda, M.; Shimomura, I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest., 2004, 114, 1752-1761.
163. Keaney, J. F. Jr.; Larson, M. G.; Vasan, R. S.; Wilson, P. W.; Lipinska, I.; Corey, D.; Massaro, J. M.; Sutherland, P.; Vita, J. A.; Benjamin, E. J.; Framingham Study. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler. Thromb. Vasc. Biol., 2003, 23, 434-439.
164. Pinkney, J. H.; Stehouwer, C. D.; Coppack, S. W.; Yudkin, J. S. Endothelial dysfunction: cause of the insulin resistance syndrome. Diabetes, 1997, 46 Suppl 2, S9-S13.
165. Haffner, S. M. The prediabetic problem: development of noninsulindependent diabetes mellitus and related abnormalities. J. Diabetes. Complications., 1997, 11, 69-76.
166. Verdecchia, P.; Reboldi, G.; Schillaci, G.; Borgioni, C.; Ciucci, A.; Telera, M. P.; Santeusanio, F.; Porcellati, C.; Brunetti, P. Circulating insulin and insulin growth factor-1 are independent determinants of left ventricular mass and geometry in essential hypertension. Circulation, 1999, 100, 1802-1807.
167. Dal Palù, C. Diabetes and arterial hypertension. Ital. Heart. J. Suppl., 2001, 2, 1170-1180.
168. Libby, P.; Ridker, P. M.; Maseri, A. Inflammation and atherosclerosis. Circulation, 2002, 105, 1135-1143.
169. Ward, N. C.; Hodgson, J. M.; Puddey, I. B.; Mori, T. A.; Beilin, L. J.; Croft, K. D. Oxidative stress in human hypertension: association with antihypertensive treatment, gender, nutrition, and lifestyle. Free Radic. Biol. Med., 2004, 36, 226-232.
170. Suthanthiran, M.; Anderson, M. E.; Sharma, V. K.; Meister, A. Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens. Proc. Natl. Acad. Sci. USA, 1990, 87, 3343-3347.
171. Pinzani, M.; Marra, F.; Carloni, V. Signal transduction in hepatic stellate cells. Liver, 1998, 18, 2-13.
172. Viel, E. C.; Benkirane, K.; Javeshghani, D.; Touyz, R. M.; Schiffrin, E. L. Xanthine oxidase and mitochondria contribute to vascular superoxide anion generation in DOCA-salt hypertensive rats. Am. J. Physiol. Heart. Circ. Physiol., 2008, 295, H281-H288.
173. Mervaala, E. M.; Cheng, Z. J.; Tikkanen, I.; Lapatto, R.; Nurminen, K.; Vapaatalo, H.; Müller, D. N.; Fiebeler, A.; Ganten, U.; Ganten, D.; Luft, F. C. Endothelial dysfunction and xanthine oxidoreductase activity in rats with human renin and angiotensinogen genes. Hypertension, 2001, 37, 414-418.
174. Lassègue, B.; Clempus, R. E. Vascular NAD (P) H oxidases: specific features, expression, and regulation. Am. J. Physiol. Regul. Integr. Comp. Physiol, 2003, 285, R277-R297.
175. Harrison, D. G.; Gongora, M. C. Oxidative stress and hypertension. Med. Clin. North. Am., 2009, 93, 621-635.
176. Callera, G. E.; Touyz, R. M.; Teixeira, S. A.; Muscara, M. N.; Carvalho, M. H.; Fortes, Z. B.; Nigro, D.; Schiffrin, E. L.; Tostes, R. C. ETA receptor blockade decreases vascular superoxide generation in DOCA-salt hypertension. Hypertension, 2003, 42, 811-817.
177. Chen, X.; Touyz, R. M.; Park, J. B.; Schiffrin, E. L. Antioxidant effects of vitamins C and E are associated with altered activation of vascular NADPH oxidase and superoxide dismutase in strokeprone SHR. Hypertension, 2001, 38, 606-611.
178. Tabet, F.; Savoia, C.; Schiffrin, E. L.; Touyz, R. M. Differential calcium regulation by hydrogen peroxide and superoxide in vascular smooth muscle cells from spontaneously hypertensive rats. J. Cardiovasc. Pharmacol., 2004, 44, 200-208.
179. Nabha, L.; Garbern, J. C.; Buller, C. L.; Charpie, J. R. Vascular oxidative stress precedes high blood pressure in spontaneously hypertensive rats. Clin. Exp. Hypertens., 2005, 27, 71-82.
180. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation, 2002, 106, 3143-3421.
181. Legro, R. S. Polycystic ovary syndrome and cardiovascular disease: a premature association? Endocr. Rev., 2003, 24, 302-312.
182. Orio, F. Jr.; Palomba, S.; Cascella, T.; De Simone, B.; Di Biase, S.; Russo, T.; Labella, D.; Zullo, F.; Lombardi, G.; Colao, A. Early impairment of endothelial structure and function in young normalweight women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 2004, 89, 4588-4593.
183. Talbott, E.; Guzick, D.; Clerici, A.; Berga, S.; Detre, K.; Weimer, K.; Kuller, L. Coronary heart disease risk factors in women with polycystic ovary syndrome. Arterioscler. Thromb. Vasc. Biol., 1995, 15, 821-826.
184. Lakhani, K.; Seifalian, A. M.; Hardiman, P. Impaired carotid viscoelastic properties in women with polycystic ovaries. Circulation, 2002, 106, 81-85.
185. Paradisi, G.; Steinberg, H. O.; Hempfling, A.; Cronin, J.; Hook, G.; Shepard, M. K.; Baron, A. D. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation, 2001, 103, 1410-1415.
186. Mather, K. J.; Verma, S.; Corenblum, B.; Anderson, T. J. Normal endothelial function despite insulin resistance in healthy women with the polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 2000, 85, 1851-1856.
187. Kelly, C. J.; Speirs, A.; Gould, G. W.; Petrie, J. R.; Lyall, H.; Connell, J. M. Altered vascular function in young women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 2002, 87, 742-746.
188. Seow, K. M.; Juan, C. C.; Wang, P. H.; Ho, L. T.; Hwang, J. L. Expression levels of vascular cell adhesion molecule-1 in young and nonobese women with polycystic ovary syndrome. Gynecol. Obstet. Invest., 2012, 73, 236-241.
189. Nasiek, M.; Kos-Kudla, B.; Ostrowska, Z.; Marek, B.; Kajdaniuk, D.; Sieminska, L.; Foltyn, W. Plasma concentration of soluble intercellular adhesion molecule-1 in women with polycystic ovary syndrome. Gynecol. Endocrinol., 2004, 19, 208-215.
190. Diamanti-Kandarakis, E.; Paterakis, T.; Alexandraki, K.; Piperi, C.; Aessopos, A.; Katsikis, I.; Katsilambros, N.; Kreatsas, G.; Panidis, D. Indices of low-grade chronic inflammation in polycystic ovary syndrome and the beneficial effect of metformin. Hum. Reprod., 2006, 21, 1426-1431.
191. Diamanti-Kandarakis, E.; Spina, G.; Kouli, C.; Migdalis, I. Increased endothelin-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy. J. Clin. Endocrinol. Metab., 2001, 86, 4666-4673.
192. Ferri, C.; Pittoni, V.; Piccoli, A.; Laurenti, O.; Cassone, M. R.; Bellini, C.; Properzi, G.; Valesini, G.; De Mattia, G.; Santucci, A. Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo. J. Clin. Endocrinol. Metab., 1995, 80, 829-835.
193. Sampson, M.; Kong, C.; Patel, A.; Unwin, R.; Jacobs, H. S. Ambulatory blood pressure profiles and plasminogen activator inhibitor (PAI-1) activity in lean women with and without the polycystic ovary syndrome. Clin. Endocrinol. (Oxf)., 1996, 45, 623-629.
194. Orio, F. Jr.; Palomba, S.; Cascella, T.; Tauchmanovà, L.; Nardo, L. G.; Di Biase, S.; Labella, D.; Russo, T.; Savastano, S.; Tolino, A.; Zullo, F.; Colao, A.; Lombardi, G. Is plasminogen activator inhibitor-1 a cardiovascular risk factor in young women with polycystic ovary syndrome? Reprod. Biomed. Online., 2004, 9, 505-510.
195. Boulman, N.; Levy, Y.; Leiba, R.; Shachar, S.; Linn, R.; Zinder, O.; Blumenfeld, Z. Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease. J. Clin. Endocrinol. Metab., 2004, 89, 2160-2165.
196. Glintborg, D.; Højlund, K.; Andersen, M.; Henriksen, J. E.; Beck-Nielsen, H.; Handberg, A. Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment. Diabetes Care., 2008, 31, 328-334.
197. Vgontzas, A. N.; Trakada, G.; Bixler, E. O.; Lin, H. M.; Pejovic, S.; Zoumakis, E.; Chrousos, G. P.; Legro, R. S. Plasma interleukin 6 levels are elevated in polycystic ovary syndrome independently of obesity or sleep apnea. Metabolism., 2006, 55, 1076-1082.
198. González, F.; Rote, N. S.; Minium, J.; Kirwan, J. P. Evidence of proatherogenic inflammation in polycystic ovary syndrome. Metabolism, 2009, 58, 954-962.
199. Toscano, V. Sindrome dell'ovaio policistico. In: Manuale di Terapia delle Malattie Endocrine e Metaboliche; Andreani, Tamburano; 2000.
200. Tsilchorozidou, T.; Overton, C.; Conway, G. S. The pathophysiology of polycystic ovary syndrome. Clin. Endocrinol. (Oxf)., 2004, 60, 1-17.
201. Mathur, R.; Alexander, C. J.; Yano, J.; Trivax, B.; Azziz, R. Use of metformin in polycystic ovary syndrome. Am. J. Obstet. Gynecol., 2008, 199, 596-609.
202. Palomba, S.; Falbo, A.; Zullo, F.; Orio, F. Jr. Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. Endocr. Rev., 2009, 30, 1-50.
203. Diamanti-Kandarakis, E.; Alexandraki, K.; Protogerou, A.; Piperi, C.; Papamichael, C.; Aessopos, A.; Lekakis, J.; Mavrikakis, M. Metformin administration improves endothelial function in women with polycystic ovary syndrome. Eur. J. Endocrinol., 2005, 152, 749-756.
204. Kuo, R. C.; Baxter, G. T.; Thompson, S. H.; Stricker, S. A.; Patton, C.; Bonaventura, J.; Epel, D. NO is necessary and sufficient for egg activation at fertilization. Nature, 2000, 406, 633-636.
205. Tao, M.; Kodama, H.; Kagabu, S.; Fukuda, J.; Murata, M.; Shimizu, Y.; Hirano, H.; Tanaka, T. Possible contribution of follicular interleukin-1beta to nitric oxide generation in human pre-ovulatory follicles. Hum. Reprod., 1997, 12, 2220-2225.
206. Anteby, E. Y.; Hurwitz, A.; Korach, O.; Revel, A.; Simon, A.; Finci-Yeheskel, Z.; Mayer, M.; Laufer, N. Human follicular nitric oxide pathway: relationship to follicular size, oestradiol concentrations and ovarian blood flow. Hum. Reprod., 1996, 11, 1947-1951.
207. Shukovski, L.; Tsafriri, A. The involvement of nitric oxide in the ovulatory process in the rat. Endocrinology, 1994, 135, 2287-2290.
208. Hesla, J. S.; Preutthipan, S.; Maguire, M. P.; Chang, T. S.; Wallach, E. E.; Dharmarajan, A. M. Nitric oxide modulates human chorionic gonadotropin-induced ovulation in the rabbit. Fertil. Steril., 1997, 67, 548-552.
209. Jablonka-Shariff, A.; Olson, L. M. The role of nitric oxide in oocyte meiotic maturation and ovulation: meiotic abnormalities of endothelial nitric oxide synthase knock-out mouse oocytes. Endocrinology, 1998, 139, 2944-2954.
210. Gregg, A. R. Mouse models and the role of nitric oxide in reproduction. Curr. Pharm. Des., 2003, 9, 391-398.
211. Yang, J. Z.; Ajonuma, L. C.; Rowlands, D. K.; Tsang, L. L.; Ho, L. S.; Lam, S. Y.; Chen, W. Y.; Zhou, C. X.; Chung, Y. W.; Cho, C. Y.; Tse, J. Y.; James, A. E.; Chan, H. C. The role of inducible nitric oxide synthase in gamete interaction and fertilization: a comparative study on knockout mice of three NOS isoforms. Cell. Biol. Int., 2005, 29, 785-791.
212. Goud, P. T.; Goud, A. P.; Diamond, M. P.; Gonik, B.; Abu-Soud, H. M. Nitric oxide extends the oocyte temporal window for optimal fertilization. Free. Radic. Biol. Med., 2008, 45, 453-459.
213. González, F.; Rote, N. S.; Minium, J.; Kirwan, J. P. Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 2006, 91, 336-340.
214. Fenkci, V.; Fenkci, S.; Yilmazer, M.; Serteser, M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil. Steril., 2003, 80, 123-127.
215. Macut, D.; Damjanovic, S.; Panidis, D.; Spanos, N.; Glisic, B.; Petakov, M.; Rousso, D.; Kourtis, A.; Bjekic, J.; Milic, N. Oxidised low-density lipoprotein concentration - early marker of an altered lipid metabolism in young women with PCOS. Eur. J. Endocrinol., 2006, 155, 131-136.
216. Barnes, R. B. The pathogenesis of polycystic ovary syndrome: lessons from ovarian stimulation studies. J. Endocrinol. Invest., 1998, 21, 567-579.
217. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet, 1999, 354, 447-455.
218. Lonn, E.; Yusuf, S.; Hoogwerf, B.; Pogue, J.; Yi, Q.; Zinman, B.; Bosch, J.; Dagenais, G.; Mann, J. F.; Gerstein, H. C.; HOPE Study; MICRO-HOPE Study. Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy. Diabetes Care, 2002, 25, 1919-1927.
219. Heller, R.; Werner-Felmayer, G.; Werner, E. R. Alpha-Tocopherol and endothelial nitric oxide synthesis. Ann. N. Y. Acad. Sci., 2004, 1031, 74-85.
220. Kris-Etherton, P. M.; Lichtenstein, A. H.; Howard, B. V.; Steinberg, D.; Witztum, J. L.; Nutrition Committee of the American Heart Association Council on Nutrition, Physical Activity, and Metabolism. Antioxidant vitamin supplements and cardiovascular disease. Circulation, 2004, 110, 637-641.
221. Parodi, O.; De Maria, R.; Roubina, E. Redox state, oxidative stress and endothelial dysfunction in heart failure: the puzzle of nitratethiol interaction. J. Cardiovasc. Med. (Hagerstown), 2007, 8, 765-774.
222. Ignarro, L. J.; Edwards, J. C.; Gruetter, D. Y.; Barry, B. K.; Gruetter, C. A. Possible involvement of S-nitrosothiols in the activation of guanylate cyclase by nitroso compounds. FEBS Lett., 1980, 110, 275-278.
223. Levy, A. S.; Vigna, C.; Rush, J. W. Glutathione enhances endotheliummediated control of coronary vascular resistance via a ROSand NO intermediate-dependent mechanism. J. Appl. Physiol. (1985)., 2012, 113, 246-254.
224. Kugiyama, K.; Ohgushi, M.; Motoyama, T.; Hirashima, O.; Soejima, H.; Misumi, K.; Yoshimura, M.; Ogawa, H.; Sugiyama, S.; Yasue, H. Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation. Circulation, 1998, 97, 2299-2301.
225. Cotgreave, I. A. N-acetylcysteine: pharmacological considerations and experimental and clinical applications. Adv. Pharmacol., 1997, 38, 205-227.
226. Kelly, G. S. Clinical applications of N-acetylcysteine. Altern. Med. Rev., 1998, 3, 114-127.
227. Anderson, M. E.; Luo, J. L. Glutathione therapy: from prodrugs to genes. Semin. Liver. Dis., 1998, 18, 415-424.
228. Marfella, R.; Verrazzo, G.; Acampora, R.; La Marca, C.; Giunta, R.; Lucarelli, C.; Paolisso, G.; Ceriello, A.; Giugliano, D. Glutathione reverses systemic hemodynamic changes induced by acute hyperglycemia in healthy subjects. Am. J. Physiol., 1995, 268, E1167-E1173.
229. Martina, V.; Bruno, G. A.; Zumpano, E.; Origlia, C.; Quaranta, L.; Pescarmona, G. P. Administration of glutathione in patients with type 2 diabetes mellitus increases the platelet constitutive nitric oxide synthase activity and reduces PAI-1. J. Endocrinol. Invest., 2001, 24, 37-41.
230. Pieper, G. M.; Siebeneich, W. Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction. J. Cardiovasc. Pharmacol., 1998, 32, 101-105.
231. Kowluru, R. A.; Tang, J.; Kern, T. S. Abnormalities of retinal metabolism in diabetes and experimental galactosemia. VII. Effect of long-term administration of antioxidants on the development of retinopathy. Diabetes., 2001, 50, 1938-1942.
232. Tsai, G. Y.; Cui, J. Z.; Syed, H.; Xia, Z.; Ozerdem, U.; McNeill, J. H.; Matsubara, J. A. Effect of N-acetylcysteine on the early expression of inflammatory markers in the retina and plasma of diabetic rats. Clin. Experiment. Ophthalmol., 2009, 37, 223-231.
233. Kamboj, S. S.; Vasishta, R. K.; Sandhir, R. N-acetylcysteine inhibits hyperglycemia-induced oxidative stress and apoptosis markers in diabetic neuropathy. J. Neurochem., 2010, 112, 77-91.
234. Recchioni, R.; Marcheselli, F.; Moroni, F.; Pieri, C. Apoptosis in human aortic endothelial cells induced by hyperglycemic condition involves mitochondrial depolarization and is prevented by Nacetyl-L-cysteine. Metabolism, 2002, 51, 1384-1388.
235. Kumar, S.; Sitasawad, S. L. N-acetylcysteine prevents glucose/glucose oxidase-induced oxidative stress, mitochondrial damage and apoptosis in H9c2 cells. Life Sci., 2009, 84, 328-336.
236. Gibson, K. R.; Winterburn, T. J.; Barrett, F.; Sharma, S.; MacRury, S. M.; Megson, I. L. Therapeutic potential of N-acetylcysteine as an antiplatelet agent in patients with type-2 diabetes. Cardiovasc. Diabetol., 2011, 10, 43.
237. De Mattia, G.; Bravi, M. C.; Laurenti, O.; Cassone-Faldetta, M.; Proietti, A.; De Luca, O.; Armiento, A.; Ferri, C. Reduction of oxidative stress by oral N-acetyl-L-cysteine treatment decreases plasma soluble vascular cell adhesion molecule-1 concentrations in non-obese, non-dyslipidaemic, normotensive, patients with noninsulindependent diabetes. Diabetologia, 1998, 41, 1392-1396.
238. Neri, S.; Signorelli, S. S.; Torrisi, B.; Pulvirenti, D.; Mauceri, B.; Abate, G.; Ignaccolo, L.; Bordonaro, F.; Cilio, D.; Calvagno, S.; Leotta, C. Effects of antioxidant supplementation on postprandial oxidative stress and endothelial dysfunction: a single-blind, 15-day clinical trial in patients with untreated type 2 diabetes, subjects with impaired glucose tolerance, and healthy controls. Clin. Ther., 2005, 27, 1764-1773.
239. Masha, A.; Brocato, L.; Dinatale, S.; Mascia, C.; Biasi, F.; Martina, V. N-acetylcysteine is able to reduce the oxidation status and the endothelial activation after a high-glucose content meal in patients with Type 2 diabetes mellitus. J. Endocrinol. Invest., 2009, 32, 352-356.
240. Ozkilic, A. C.; Cengiz, M.; Ozaydin, A.; Cobanoglu, A.; Kanigur, G. The role of N-acetylcysteine treatment on anti-oxidative status in patients with type II diabetes mellitus. J. Basic. Clin. Physiol. Pharmacol., 2006, 17, 245-254.
241. Martina, V.; Masha, A.; Ramella Gigliardi, V.; Brocato, L.; Manzato, E.; Berchio, A.; Massarenti, P.; Settanni, F.; Della Casa, L.; Bergamini, S.; Iannone, A. Long-term N-acetylcysteine and Larginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes. Diabetes Care, 2008, 31, 940-944.
242. Darmaun, D.; Smith, S. D.; Sweeten, S.; Hartman, B. K.; Welch, S.; Mauras, N. Poorly controlled type 1 diabetes is associated with altered glutathione homeostasis in adolescents: apparent resistance to N-acetylcysteine supplementation. Pediatr. Diabetes, 2008, 9, 577-582.
243. Saklayen, M. G.; Yap, J.; Vallyathan, V. Effect of month-long treatment with oral N-acetylcysteine on the oxidative stress and proteinuria in patients with diabetic nephropathy: a pilot study. J. Investig. Med., 2010, 58, 28-31.
244. Treweeke, A. T.; Winterburn, T. J.; Mackenzie, I.; Barrett, F.; Barr, C.; Rushworth, G. F.; Dransfield, I.; MacRury, S. M.; Megson, I. L. N-Acetylcysteine inhibits platelet-monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial. Diabetologia, 2012, 55, 2920-2928.
245. Bouloumie, A.; Marumo, T.; Lafontan, M.; Busse, R. Leptin induces oxidative stress in human endothelial cells. FASEB J., 1999, 13, 1231-1238.
246. Kim, J. R.; Ryu, H. H.; Chung, H. J.; Lee, J. H.; Kim, S. W.; Kwun, W. H.; Baek, S. H.; Kim, J. H. Association of anti-obesity activity of N-acetylcysteine with metallothionein-II down-regulation. Exp. Mol. Med., 2006, 38, 162-172.
247. Calzadilla, P.; Sapochnik, D.; Cosentino, S.; Diz, V.; Dicelio, L.; Calvo, J. C.; Guerra, L. N. N-Acetylcysteine Reduces Markers of Differentiation in 3T3-L1 Adipocytes. Int. J. Mol. Sci., 2011, 12, 6936-6951.
248. Araki, S.; Dobashi, K.; Kubo, K.; Yamamoto, Y.; Asayama, K.; Shirahata, A. N-acetylcysteine attenuates TNF-alpha induced changes in secretion of interleukin-6, plasminogen activator inhibitor-1 and adiponectin from 3T3-L1 adipocytes. Life Sci., 2006, 79, 2405-2412.
249. Diniz, Y. S.; Rocha, K. K.; Souza, G. A.; Galhardi, C. M.; Ebaid, G. M.; Rodrigues, H. G.; Novelli Filho, J. L.; Cicogna, A. C.; Novelli, E. L. Effects of N-acetylcysteine on sucrose-rich diet-induced hyperglycaemia, dyslipidemia and oxidative stress in rats. Eur. J. Pharmacol., 2006, 543, 151-157.
250. Novelli, E. L.; Santos, P. P.; Assalin, H. B.; Souza, G.; Rocha, K.; Ebaid, G. X.; Seiva, F. R.; Mani, F.; Fernandes, A. A. Nacetylcysteine in high-sucrose diet-induced obesity: energy expenditure and metabolic shifting for cardiac health. Pharmacol. Res., 2009, 59, 74-79.
251. Souza, G. A.; Ebaid, G. X.; Seiva, F. R.; Rocha, K. H.; Galhardi, C. M.; Mani, F.; Novelli, E. L. N-acetylcysteine an allium plant compound improves high-sucrose diet-induced obesity and related effects. Evid. Based. Complement. Alternat. Med., 2011, 643269.
252. Wang, T.; Si, Y.; Shirihai, O. S.; Si, H.; Schultz, V.; Corkey, R. F.; Hu, L.; Deeney, J. T.; Guo, W.; Corkey, B. E. Respiration in adipocytes is inhibited by reactive oxygen species. Obesity (Silver Spring)., 2010, 18, 1493-1502.
253. Chang, Y. C.; Yu, Y. H.; Shew, J. Y.; Lee, W. J.; Hwang, J. J.; Chen, Y. H.; Chen, Y. R.; Wei, P. C.; Chuang, L. M.; Lee, W. H. Deficiency of NPGPx, an oxidative stress sensor, leads to obesity in mice and human. EMBO Mol. Med., 2013, 5, 1165-1179.
254. Calzadilla, P.; Gómez-Serrano, M.; García-Santos, E.; Schiappacasse, A.; Abalde, Y.; Calvo, J. C.; Peral, B.; Guerra, L. N. NAcetylcysteine affects obesity-related protein expression in 3T3-L1 adipocytes. Redox. Rep., 2013, 18, 210-218.
255. Ruiz, F. J.; Salom, M. G.; Inglés, A. C.; Quesada, T.; Vicente, E.; Carbonell, L. F. N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs. Am. J. Physiol., 1994, 267, R767-R772.
256. Cabassi, A.; Dumont, E. C.; Girouard, H.; Bouchard, J. F.; Le Jossec, M.; Lamontagne, D.; Besner, J. G.; De Champlain, J. Effects of chronic N-acetylcysteine treatment on the actions of peroxynitrite on aortic vascular reactivity in hypertensive rats. J. Hypertens., 2001, 19, 1233-1244.
257. Girouard, H.; Chulak, C.; Wu, L.; Lejossec, M.; De Champlain, J. N-acetylcysteine improves nitric oxide and alpha-adrenergic pathways in mesenteric beds of spontaneously hypertensive rats. Am. J. Hypertens., 2003, 16, 577-584.
258. Pechánová, O.; Zicha, J.; Paulis, L.; Zenebe, W.; Dobesová, Z.; Kojsová, S.; Jendeková, L.; Sládková, M.; Dovinová, I.; Simko, F.; Kunes, J. The effect of N-acetylcysteine and melatonin in adult spontaneously hypertensive rats with established hypertension. Eur. J. Pharmacol., 2007, 561, 129-136.
259. Vasdev, S.; Mian, T.; Ford, C. A.; Longerich, L.; Parai, S. Role of endogenous aldehydes in spontaneously hypertensive and disulfiraminduced hypertensive rats. Nutr. Metab. Cardiovasc. Dis., 1996, 6, 130-140.
260. Pechánová, O.; Zicha, J.; Kojsová, S.; Dobesová, Z.; Jendeková, L.; Kunes, J. Effect of chronic N-acetylcysteine treatment on the development of spontaneous hypertension. Clin. Sci. (Lond)., 2006, 110, 235-242.
261. Zhang, L.; Fujii, S.; Igarashi, J.; Kosaka, H. Effects of thiol antioxidant on reduced nicotinamide adenine dinucleotide phosphate oxidase in hypertensive Dahl salt-sensitive rats. Free. Radic. Biol. Med., 2004, 37, 1813-1820.
262. Rauchová, H.; Pechánová, O.; Kunes, J.; Vokurková, M.; Dobesová, Z.; Zicha, J. Chronic N-acetylcysteine administration prevents development of hypertension in N (omega)-nitro-L-arginine methyl ester-treated rats: the role of reactive oxygen species. Hypertens. Res., 2005, 28, 475-482.
263. Suárez, C.; Del Arco, C.; Lahera, V.; Ruilope, L. M. Nacetylcysteine potentiates the antihypertensive effect of angiotensin converting enzyme inhibitors. Am. J. Hypertens., 1995, 8, 859.
264. Barrios, V.; Calderón, A.; Navarro-Cid, J.; Lahera, V.; Ruilope, L. M. N-acetylcysteine potentiates the antihypertensive effect of ACE inhibitors in hypertensive patients. Blood Press., 2002, 11, 235-239.
265. Zeng, G.; Nystrom, F. H.; Ravichandran, L. V.; Cong, L. N.; Kirby, M.; Mostowski, H.; Quon, M. J. Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation, 2000, 101, 1539-1545.
266. Montagnani, M.; Ravichandran, L. V.; Chen, H.; Esposito, D. L.; Quon, M. J. Insulin receptor substrate-1 and phosphoinositidedependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells. Mol. Endocrinol., 2002, 16, 1931-1942.
267. Blouet, C.; Mariotti, F.; Azzout-Marniche, D.; Mathé, V.; Mikogami, T.; Tomé, D.; Huneau, J. F. Dietary cysteine alleviates sucroseinduced oxidative stress and insulin resistance. Free. Radic. Biol. Med., 2007, 42, 1089-1097.
268. Song, D.; Hutchings, S.; Pang, C. C. Chronic N-acetylcysteine prevents fructose-induced insulin resistance and hypertension in rats. Eur. J. Pharmacol., 2005, 508, 205-210.
269. Vasdev, S.; Ford, C. A.; Longerich, L.; Gadag, V.; Wadhawan, S. Role of aldehydes in fructose induced hypertension. Mol. Cell. Biochem., 1998, 181, 1-9.
270. Lavis, V. R.; Williams, R. H. Studies of the insulin-like actions of thiols upon isolated fat cells. J. Biol. Chem., 1970, 245, 23-31.
271. Gazit, V.; Ben-Abraham, R.; Vofsi, O.; Katz, Y. L-cysteine increases glucose uptake in mouse soleus muscle and SH-SY5Y cells. Metab. Brain Dis., 2003, 18, 221-231.
272. Ammon, H. P.; Müller, P. H.; Eggstein, M.; Wintermantel, C.; Aigner, B.; Safayhi, H.; Stützle, M.; Renn, W. Increase in glucose consumption by acetylcysteine during hyperglycemic clamp. A study with healthy volunteers. Arzneimittelforschung, 1992, 42, 642-645.
273. Hildebrandt, W.; Hamann, A.; Krakowski-Roosen, H.; Kinscherf, R.; Dugi, K.; Sauer, R.; Lacher, S.; Nöbel, N.; Bodens, A.; Bellou, V.; Edler, L.; Nawroth, P.; Dröge, W. Effect of thiol antioxidant on body fat and insulin reactivity. J. Mol. Med. (Berl)., 2004, 82, 336-344.
274. Fulghesu, A. M.; Ciampelli, M.; Muzj, G.; Belosi, C.; Selvaggi, L.; Ayala, G. F.; Lanzone, A. N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil. Steril., 2002, 77, 1128-1135.
275. Masha, A.; Manieri, C.; Dinatale, S.; Bruno, G. A.; Ghigo, E.; Martina, V. Prolonged treatment with N-acetylcysteine and L-arginine restores gonadal function in patients with polycystic ovary syndrome. J. Endocrinol. Invest., 2009, 32, 870-872.
276. Elnashar, A.; Fahmy, M.; Mansour, A.; Ibrahim, K. N-acetyl cysteine vs. metformin in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective randomized controlled study. Fertil. Steril., 2007, 88, 406-409.
277. Rizk, A. Y.; Bedaiwy, M. A.; Al-Inany, H. G. N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome. Fertil. Steril., 2005, 83, 367-370.
278. Badawy, A.; State, O.; Abdelgawad, S. N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. Acta Obstet. Gynecol. Scand., 2007, 86, 218-222.
279. Salehpour, S.; Sene, A. A.; Saharkhiz, N.; Sohrabi, M. R.; Moghimian, F. N-Acetylcysteine as an adjuvant to clomiphene citrate for successful induction of ovulation in infertile patients with polycystic ovary syndrome. J. Obstet. Gynaecol. Res., 2012, 38, 1182-1186.
280. Oner, G.; Muderris, I. I. Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol., 2011, 159, 127-131.
281. Abu Hashim, H.; Anwar, K.; El-Fatah, R. A. N-acetyl cysteine plus clomiphene citrate versus metformin and clomiphene citrate in treatment of clomiphene-resistant polycystic ovary syndrome: a randomized controlled trial. J. Womens. Health. (Larchmt)., 2010, 19, 2043-2048.