Advances in pharmacologic modulation of nitric oxide in hypertension

Current Cardiology Reports

Volumn 12, Issue 6, 2010, Pages 472-480

  Mizuno, Yoshiko ^a,b   Jacob, Robert F ^b   Mason, R Preston ^a,b  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b ELUCIDA RESEARCH LLC   (United States)

Author keywords

Antihypertensives; Central aortic pressure; Endothelial function; Nitric oxide

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ALDOSTERONE ANTAGONIST; ALISKIREN; AMLODIPINE; ANGIOTENSIN RECEPTOR ANTAGONIST; BENAZEPRIL; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; CARVEDILOL; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; ENALAPRIL; EPLERENONE; GLYCERYL TRINITRATE; HYDRALAZINE; HYDROCHLOROTHIAZIDE; ISOSORBIDE DINITRATE; ISOSORBIDE MONONITRATE; LIPOSOME; MINERALOCORTICOID ANTAGONIST; NEBIVOLOL; NIFEDIPINE; NITRIC OXIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; SILDENAFIL; SPIRONOLACTONE; SUPEROXIDE DISMUTASE; TADALAFIL; TELMISARTAN; UNINDEXED DRUG;

ALDOSTERONE RELEASE; ANGINA PECTORIS; ANTIHYPERTENSIVE ACTIVITY; CARDIOVASCULAR RISK; CLINICAL TRIAL; CORONARY ARTERY DISEASE; DISEASE ASSOCIATION; DISEASE MARKER; DOSE RESPONSE; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; ENDOTHELIAL DYSFUNCTION; ENZYME ACTIVITY; ESSENTIAL HYPERTENSION; HEADACHE; HEART DISEASE; HEART FAILURE; HIGH RISK POPULATION; HORMONE ACTION; HUMAN; HYPERGLYCEMIA; HYPERLIPIDEMIA; HYPERTENSION; HYPOTENSION; INFLAMMATION; INSULIN RESISTANCE; LIPOSOMAL DELIVERY; NONHUMAN; PHARMACOLOGICAL BLOCKING; PREDICTION; PULSE PRESSURE; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SYSTOLIC HYPERTENSION; VASCULAR DISEASE;

ADRENERGIC BETA-ANTAGONISTS; ANTIHYPERTENSIVE AGENTS; BIOLOGICAL AVAILABILITY; CALCIUM CHANNEL BLOCKERS; ENDOTHELIUM, VASCULAR; HEMODYNAMICS; HUMANS; HYPERTENSION; INSULIN RESISTANCE; NITRIC OXIDE; PHOSPHODIESTERASE INHIBITORS; RENIN-ANGIOTENSIN SYSTEM; RISK FACTORS;

EID: 77958464682     PISSN: 15233782     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11886-010-0142-5     Document Type: Review

References (67)

1. T Weber J Auer MF O'Rourke, et al. 2004 Arterial stiffness, wave reflections, and the risk of coronary artery disease Circulation 109 184 189 10.1161/01.CIR.0000105767.94169.E3 14662706 (Pubitemid 38114137)
2. B Williams PS Lacy SM Thom, et al. 2006 Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study Circulation 113 1213 1225 1:CAS:528:DC%2BD28XhvVektrg%3D 10.1161/CIRCULATIONAHA. 105.606962 16476843 (Pubitemid 43948020)
3. DG Harrison 1997 Cellular and molecular mechanisms of endothelial cell dysfunction J Clin Invest 100 2153 2157 1:CAS:528:DyaK2sXnt1Ggs74%3D 10.1172/JCI119751 9410891
4. JA Panza AA Quyyumi JE Brush Jr 1990 Epstein SE: Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension N Engl J Med 323 22 27 1:STN:280:DyaK3c3oslagug%3D%3D 10.1056/NEJM199007053230105 2355955
5. H Kinoshita S Milstien C Wambi ZS Katusic 1997 Inhibition of tetrahydrobiopterin biosynthesis impairs endothelial dependent relaxation in canine basilar artery Am J Physiol 273 H718 H724 1:CAS:528:DyaK2sXls12mu7s%3D 9277488
6. U Landmesser S Dikalov SR Price, et al. 2003 Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension J Clin Invest 111 1201 1209 1:CAS:528: DC%2BD3sXjtFCrs7o%3D 12697739
7. U Landmesser H Cai S Dikalov, et al. 2002 Role of p47(phox) in vascular oxidative stress and hypertension caused by angiotensin II Hypertension 40 511 515 1:CAS:528:DC%2BD38Xntlamsrs%3D 10.1161/01.HYP.0000032100.23772.98 12364355
8. RP Mason R Kubant RF Jacob, et al. 2009 Loss of arterial and renal nitric oxide bioavailability in hypertensive rats with diabetes: effect of beta-blockers Am J Hypertens 22 1160 1166 10.1038/ajh.2009.163 19730416 This is an original article showing the effect of multiple risk factors on endothelial dysfunction and metabolic disease
9. RP Mason L Kalinowski RF Jacob, et al. 2005 Nebivolol reduces nitroxidative stress and restores nitric oxide bioavailability in endothelium of black Americans Circulation 112 3795 3801 1:CAS:528:DC%2BD2MXht1yitb7O 10.1161/CIRCULATIONAHA.105.556233 16330685 (Pubitemid 43739521)
10. U Campia WK Choucair MB Bryant, et al. 2002 Reduced endothelium-dependent and -independent dilation of conductance arteries in African Americans J Am Coll Cardiol 40 754 760 1:CAS:528:DC%2BD38XntVGqu7k%3D 10.1016/S0735-1097(02) 02015-6 12204507 (Pubitemid 34925623)
11. J Redon MR Oliva C Tormos, et al. 2003 Antioxidant activities and oxidative stress byproducts in human hypertension Hypertension 41 1096 1101 1:CAS:528:DC%2BD3sXjtFWqtbs%3D 10.1161/01.HYP.0000068370.21009.38 12707286 (Pubitemid 36548609)
12. B Rodriguez-Iturbe CD Zhan Y Quiroz, et al. 2003 Antioxidant-rich diet relieves hypertension and reduces renal immune infiltration in spontaneously hypertensive rats Hypertension 41 341 346 1:CAS:528:DC%2BD3sXnsFSntg%3D%3D 10.1161/01.HYP.0000052833.20759.64 12574105 (Pubitemid 36204912)
13. SA Cooper A Whaley-Connell J Habibi, et al. 2007 Renin-angiotensin- aldosterone system and oxidative stress in cardiovascular insulin resistance Am J Physiol Heart Circ Physiol 293 H2009 H2023 1:CAS:528:DC%2BD2sXht1WlurrF 10.1152/ajpheart.00522.2007 17586614 This is a comprehensive review on oxidative stress, cardiovascular insulin resistance, and the contribution of Ang II to insulin/IGF-1 signaling pathways (Pubitemid 47605846)
14. JB Laursen S Rajagopalan Z Galis, et al. 1997 Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension Circulation 95 588 593 1:CAS:528:DyaK2sXhsVCis7c%3D 9024144
15. H Thai J Wollmuth S Goldman M Gaballa 2003 Angiotensin subtype 1 receptor (AT1) blockade improves vasorelaxation in heart failure by up-regulation of endothelial nitric-oxide synthase via activation of the AT2 receptor J Pharmacol Exp Ther 307 1171 1178 1:CAS:528:DC%2BD3sXpslSht7w%3D 10.1124/jpet.103.054916 14560036 (Pubitemid 37494239)
16. M Takemoto K Egashira M Usui, et al. 1997 Important role of tissue angiotensin-converting enzyme activity in the pathogenesis of coronary vascular and myocardial structural changes induced by long-term blockade of nitric oxide synthesis in rats J Clin Invest 99 278 287 1:CAS:528:DyaK2sXntVyhug%3D%3D 10.1172/JCI119156 9005996
17. AH Gradman R Kad 2008 Renin inhibition in hypertension J Am Coll Cardiol 51 519 528 1:CAS:528:DC%2BD1cXhsFygsLc%3D 10.1016/j.jacc.2007.10.027 18237679 This is an insightful review focusing on the structure and function of renin and prorenin along with the efficacy of aliskiren
18. E O'Brien J Barton J Nussberger, et al. 2007 Aliskiren reduces blood pressure and suppresses plasma renin activity in combination with a thiazide diuretic, an angiotensin-converting enzyme inhibitor, or an angiotensin receptor blocker Hypertension 49 276 284 10.1161/01.HYP.0000253780.36691.4f 17159081 This is a clinical study describing the effects of aliskiren on plasma renin activity in combination therapy with other RAS-directed treatments (Pubitemid 46143002)
19. T Imanishi H Tsujioka H Ikejima, et al. 2008 Renin inhibitor aliskiren improves impaired nitric oxide bioavailability and protects against atherosclerotic changes Hypertension 52 563 572 1:CAS:528:DC%2BD1cXpvFKgs7o%3D 10.1161/HYPERTENSIONAHA.108.111120 18645051 This is a recent study showing an antioxidant effect of combined treatment with aldosterone antagonist and ACE inhibitor
20. G Nguyen AH Danser 2006 The (pro)renin receptor: therapeutic consequences Expert Opin Investig Drugs 15 1131 1135 1:CAS:528:DC%2BD28XpvVeisLg%3D 10.1517/13543784.15.10.1131 16989589 (Pubitemid 44608252)
21. EL Schiffrin 2006 Effects of aldosterone on the vasculature Hypertension 47 312 318 1:CAS:528:DC%2BD28Xht1Cmsbg%3D 10.1161/01.HYP.0000201443.63240.a7 16432039 (Pubitemid 43740260)
22. B Pitt F Zannad WJ Remme, et al. 1999 The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators N Engl J Med 341 709 717 1:CAS:528:DyaK1MXmtVyrurk%3D 10.1056/NEJM199909023411001 10471456 (Pubitemid 29407370)
23. CA Farquharson AD Struthers 2000 Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure Circulation 101 594 597 1:CAS:528:DC%2BD3cXhtlGntL4%3D 10673249
24. A Virdis MF Neves F Amiri, et al. 2002 Spironolactone improves angiotensin-induced vascular changes and oxidative stress Hypertension 40 504 510 1:CAS:528:DC%2BD38Xntlams7Y%3D 10.1161/01.HYP.0000034738.79310.06 12364354
25. D Nagata M Takahashi K Sawai, et al. 2006 Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity Hypertension 48 165 171 1:CAS:528:DC%2BD28XlvVSmtL4%3D 10.1161/01.HYP. 0000226054.53527.bb 16754797 (Pubitemid 44297539)
26. T Imanishi H Ikejima H Tsujioka, et al. 2008 Addition of eplerenone to an angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability Hypertension 51 734 741 1:CAS:528:DC%2BD1cXhvVems7s%3D 10.1161/HYPERTENSIONAHA.107.104299 18227404 This is the initial study describing the effects of aliskiren on NO bioavailability (Pubitemid 351301528)
27. H Oberleithner C Callies K Kusche-Vihrog, et al. 2009 Potassium softens vascular endothelium and increases nitric oxide release Proc Natl Acad Sci U S A 106 2829 2834 1:CAS:528:DC%2BD1MXislaht7k%3D 10.1073/pnas.0813069106 19202069
28. SL Liu S Schmuck JZ Chorazcyzewski, et al. 2003 Aldosterone regulates vascular reactivity: short-term effects mediated by phosphatidylinositol 3-kinase-dependent nitric oxide synthase activation Circulation 108 2400 2406 1:CAS:528:DC%2BD3sXos1Snu7o%3D 10.1161/01.CIR.0000093188.53554.44 14557368 (Pubitemid 37413549)
29. McTavish D, Campoli-Richards D, Sorkin EM: Carvedilol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs 1993, 45:232-258. (Pubitemid 23092628)
30. J Lee M Lee JU Kim, et al. 2005 Carvedilol reduces plasma 8-hydroxy-2'-deoxyguanosine in mild to moderate hypertension: a pilot study Hypertension 45 986 990 1:CAS:528:DC%2BD2MXjtlyls74%3D 10.1161/01.HYP. 0000164569.63160.24 15837835 (Pubitemid 40628948)
31. T Yoshioka N Iwamoto F Tsukahara, et al. 2000 Anti-NO action of carvedilol in cell-free system and in vascular endothelial cells Br J Pharmacol 129 1530 1535 1:CAS:528:DC%2BD3cXisVyltLs%3D 10.1038/sj.bjp.0703241 10742311
32. Van de Water A 1988 Xhonneux R, Reneman RS, Janssen PA: Cardiovascular effects of dl-nebivolol and its enantiomers-a comparison with those of atenolol Eur J Pharmacol 156 95 103 10.1016/0014-2999(88)90151-3 3208842
33. R Troost E Schwedhelm S Rojczyk, et al. 2000 Nebivolol decreases systemic oxidative stress in healthy volunteers Br J Pharmacol 50 377 379 1:CAS:528:DC%2BD3cXnvV2gsbg%3D
34. H Mollnau E Schulz A Daiber, et al. 2003 Nebivolol prevents vascular NOS III uncoupling in experimental hyperlipidemia and inhibits NADPH oxidase activity in inflammatory cells Arterioscler Thromb Vasc Biol 23 615 621 1:CAS:528:DC%2BD3sXisFKgtbs%3D 10.1161/01.ATV.0000065234.70518.26 12692005 (Pubitemid 36438074)
35. L Kalinowski LW Dobrucki M Szczepanska-Konkel, et al. 2003 Third-generation beta-blockers stimulate nitric oxide release from endothelial cells through ATP efflux: a novel mechanism for antihypertensive action Circulation 107 2747 2752 1:CAS:528:DC%2BD3sXjvFKjtbs%3D 10.1161/01.CIR. 0000066912.58385.DE 12742996
36. C Dessy J Saliez P Ghisdal, et al. 2005 Endothelial beta3-adrenoreceptors mediate nitric oxide-dependent vasorelaxation of coronary microvessels in response to the third-generation beta-blocker nebivolol Circulation 112 1198 1205 1:CAS:528:DC%2BD2MXnvFyltLY%3D 10.1161/CIRCULATIONAHA.104.532960 16116070 (Pubitemid 41216127)
37. E Perez-Reyes 2003 Molecular physiology of low-voltage-activated t-type calcium channels Physiol Rev 83 117 161 1:CAS:528:DC%2BD3sXntlGgsA%3D%3D 12506128
38. G Kojda W Klaus G Werner U Fricke 1990 Reduced responses of nitrendipine in PGF2 alpha-precontracted porcine isolated arteries after pretreatment with methylene blue Basic Res Cardiol 85 461 466 1:STN:280:DyaK3M7htlWjtw%3D%3D 10.1007/BF01931492 2275701
39. VV Brovkovych L Kalinowski R Muller-Peddinghaus T Malinski 2001 Synergistic antihypertensive effects of nifedipine on endothelium: concurrent release of NO and scavenging of superoxide Hypertension 37 34 39 1:CAS:528:DC%2BD3MXosVCrsA%3D%3D 11208753
40. S Taddei A Virdis L Ghiadoni, et al. 2001 Restoration of nitric oxide availability after calcium antagonist treatment in essential hypertension Hypertension 37 943 948 1:CAS:528:DC%2BD3MXitFemsL0%3D 11244022
41. Effect of nifedipine and cerivastatin on coronary endothelial function in patients with coronary artery disease: the ENCORE I Study (Evaluation of Nifedipine and Cerivastatin On Recovery of coronary Endothelial function) [no authors listed]. Circulation 2003, 107:422-428.
42. N Kobayashi H Yanaka A Tojo, et al. 1999 Effects of amlodipine on nitric oxide synthase mRNA expression and coronary microcirculation in prolonged nitric oxide blockade-induced hypertensive rats J Cardiovasc Pharmacol 34 173 181 1:CAS:528:DyaK1MXkvV2jt78%3D 10.1097/00005344-199908000-00001 10445667 (Pubitemid 29350497)
43. X Zhang TH Hintze 1998 Amlodipine releases nitric oxide from canine coronary microvessels: an unexpected mechanism of action of a calcium channel-blocking agent Circulation 97 576 580 1:CAS:528:DyaK1cXhsVGrsLs%3D 9494028
44. K Jamerson MA Weber GL Bakris, et al. 2008 Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients N Engl J Med 359 2417 2428 1:CAS:528:DC%2BD1cXhsVCrurjJ 10.1056/NEJMoa0806182 19052124
45. LJ Ignarro C Napoli J Loscalzo 2002 Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide: an overview Circ Res 90 21 28 1:CAS:528:DC%2BD38XotFWhtA%3D%3D 10.1161/hh0102.102330 11786514 (Pubitemid 34074604)
46. RP Mason JR Cockcroft 2006 Targeting nitric oxide with drug therapy J Clin Hypertens 8 40 52 1:CAS:528:DC%2BD2sXjt1ajsA%3D%3D 10.1111/j.1524-6175. 2006.06041.x
47. AL Taylor S Ziesche C Yancy, et al. 2004 Combination of isosorbide dinitrate and hydralazine in blacks with heart failure N Engl J Med 351 2049 2057 1:CAS:528:DC%2BD2cXpslegsrs%3D 10.1056/NEJMoa042934 15533851 (Pubitemid 39482498)
48. GS Stokes AJ Bune N Huon ES Barin 2005 Long-term effectiveness of extended-release nitrate for the treatment of systolic hypertension Hypertension 45 380 384 1:CAS:528:DC%2BD2MXhtlOit74%3D 10.1161/01.HYP.0000156746.25300.1c 15699445 (Pubitemid 40315807)
49. L Zhao NA Mason JW Strange, et al. 2003 Beneficial effects of phosphodiesterase 5 inhibition in pulmonary hypertension are influenced by natriuretic Peptide activity Circulation 107 234 237 1:CAS:528: DC%2BD3sXjt1Cntw%3D%3D 10.1161/01.CIR.0000050653.10758.6B 12538421 (Pubitemid 36135217)
50. TJ Bivalacqua MF Usta HC Champion, et al. 2004 Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats Int J Impot Res 16 21 29 1:CAS:528: DC%2BD2cXhtlWksrY%3D 10.1038/sj.ijir.3901054 14963467 (Pubitemid 38401555)
51. D Kim T Aizawa H Wei, et al. 2005 Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: a mechanism by which angiotensin II antagonizes cGMP signaling J Mol Cell Cardiol 38 175 184 1:CAS:528:DC%2BD2cXhtFGgs7rF 10.1016/j.yjmcc.2004.10.013 15623434 (Pubitemid 40038664)
52. JD MacPherson TD Gillespie HA Dunkerley, et al. 2006 Inhibition of phosphodiesterase 5 selectively reverses nitrate tolerance in the venous circulation J Pharmacol Exp Ther 317 188 195 1:CAS:528:DC%2BD28XjsVWmt7s%3D 10.1124/jpet.105.094763 16330494
53. E Ferrannini A Natali B Capaldo, et al. 1997 Insulin resistance, hyperinsulinemia, and blood pressure: role of age and obesity. European Group for the Study of Insulin Resistance (EGIR) Hypertension 30 1144 1149 1:STN:280:DyaK1c%2FjsVajsw%3D%3D 9369268
54. MF Saad M Rewers J Selby, et al. 2004 Insulin resistance and hypertension: the Insulin Resistance Atherosclerosis study Hypertension 43 1324 1331 1:CAS:528:DC%2BD2cXktFSlu7k%3D 10.1161/01.HYP.0000128019.19363.f9 15123571 (Pubitemid 38691757)
55. G Zeng FH Nystrom LV Ravichandran, et al. 2000 Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells Circulation 101 1539 1545 1:CAS:528:DC%2BD3cXivVyhtr4%3D 10747347
56. H Abe N Yamada K Kamata, et al. 1998 Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1 J Clin Invest 101 1784 1788 1:CAS:528:DyaK1cXisV2qsbs%3D 10.1172/JCI1594 9541510
57. Y Wei JR Sowers R Nistala, et al. 2006 Angiotensin II-induced NADPH oxidase activation impairs insulin signaling in skeletal muscle cells J Biol Chem 281 35137 35146 1:CAS:528:DC%2BD28XhtF2gtbfN 10.1074/jbc.M601320200 16982630 (Pubitemid 46036553)
58. F Andreozzi E Laratta A Sciacqua, et al. 2004 Angiotensin II impairs the insulin signaling pathway promoting production of nitric oxide by inducing phosphorylation of insulin receptor substrate-1 on Ser312 and Ser616 in human umbilical vein endothelial cells Circ Res 94 1211 1218 1:CAS:528: DC%2BD2cXjs1yltbk%3D 10.1161/01.RES.0000126501.34994.96 15044323 (Pubitemid 38656407)
59. Y Wei AT Whaley-Connell K Chen, et al. 2007 NADPH oxidase contributes to vascular inflammation, insulin resistance, and remodeling in the transgenic (mRen2) rat Hypertension 50 384 391 1:CAS:528:DC%2BD2sXnsFOjsbw%3D 10.1161/HYPERTENSIONAHA.107.089284 17533199 This is an influential paper demonstrating the crucial role of Ang II/NAD(P)H oxidase in insulin resistance and endothelial dysfunction (Pubitemid 47205789)
60. Y Taniyama H Hitomi A Shah, et al. 2005 Mechanisms of reactive oxygen species-dependent downregulation of insulin receptor substrate-1 by angiotensin II Arterioscler Thromb Vasc Biol 25 1142 1147 1:CAS:528:DC%2BD2MXksVWqt7c%3D 10.1161/01.ATV.0000164313.17167.df 15802620 (Pubitemid 40776600)
61. H Hitomi H Kiyomoto A Nishiyama, et al. 2007 Aldosterone suppresses insulin signaling via the downregulation of insulin receptor substrate-1 in vascular smooth muscle cells Hypertension 50 750 755 1:CAS:528: DC%2BD2sXhtVCrt7jE 10.1161/HYPERTENSIONAHA.107.093955 17646573 (Pubitemid 47442741)
62. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 2003 Report of the expert committee on the diagnosis and classification of diabetes mellitus Diabetes Care 26 Suppl 1 S5 S20
63. G Lastra-Lastra JR Sowers K Restrepo-Erazo, et al. 2009 Role of aldosterone and angiotensin II in insulin resistance: an update Clin Endocrinol 71 1 6 1:CAS:528:DC%2BD1MXosl2jsr4%3D 10.1111/j.1365-2265.2008.03498.x This is a recent review describing the role of Ang II and aldosterone in the pathogenesis of insulin resistance
64. MJ Ryan SP Didion S Mathur, et al. 2004 PPAR(gamma) agonist rosiglitazone improves vascular function and lowers blood pressure in hypertensive transgenic mice Hypertension 43 661 666 1:CAS:528:DC%2BD2cXhtlynt7Y%3D 10.1161/01.HYP.0000116303.71408.c2 14744930 (Pubitemid 38282444)
65. S Fujishima Y Ohya Y Nakamura, et al. 1998 Troglitazone, an insulin sensitizer, increases forearm blood flow in humans Am J Hypertens 11 1134 1137 1:CAS:528:DyaK1cXmt1Khsbo%3D 10.1016/S0895-7061(98)00130-7 9752901 (Pubitemid 28451919)
66. JJ Nolan B Ludvik P Beerdsen, et al. 1994 Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone N Engl J Med 331 1188 1193 1:STN:280:DyaK2M%2FitFGlsw%3D%3D 10.1056/ NEJM199411033311803 7935656 (Pubitemid 24331336)
67. SC Benson HA Pershadsingh CI Ho, et al. 2004 Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity Hypertension 43 993 1002 1:CAS:528: DC%2BD2cXjt1GmtrY%3D 10.1161/01.HYP.0000123072.34629.57 15007034 (Pubitemid 38579904)