Nitric oxide synthases in heart failure

Antioxidants and Redox Signaling

Volumn 18, Issue 9, 2013, Pages 1078-1099

  Carnicer, Ricardo ^a   Crabtree, Mark J ^a   Sivakumaran, Vidhya ^b   Casadei, Barbara ^a   Kass, David A ^b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGINASE; NITRIC OXIDE SYNTHASE;

ANGIOGENESIS; AUTOCRINE EFFECT; BIOSYNTHESIS; CALCIUM CELL LEVEL; ENDOTHELIUM CELL; ENZYME ACTIVITY; GENE DELETION; HEART ARRHYTHMIA; HEART FAILURE; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HEART TRANSPLANTATION; HEART VENTRICLE HYPERTROPHY; HUMAN; METABOLISM; MITOCHONDRIAL RESPIRATION; NONHUMAN; OXYGEN CONSUMPTION; PARACRINE SIGNALING; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW;

ANIMALS; ARGINASE; AUTOCRINE COMMUNICATION; BIOPTERIN; CALCIUM SIGNALING; CYCLIC GMP; DIABETES MELLITUS; DISEASE PROGRESSION; ENZYME ACTIVATION; ENZYME INDUCTION; HEART DISEASES; HEART FAILURE; HUMANS; HYPERTENSION; MYOCARDIUM; MYOCYTES, CARDIAC; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PARACRINE COMMUNICATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STRUCTURE, TERTIARY; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; SUPEROXIDES;

EID: 84874038394     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2012.4824     Document Type: Review

References (261)

1. Adachi T. Modulation of vascular sarco/endoplasmic re-ticulum calcium ATPase in cardiovascular pathophysi-ology. Adv Pharmacol 59: 165-195, 2010.
2. Adamo CM, Dai DF, Percival JM, Minami E, Willis MS, Patrucco E, Froehner SC, and Beavo JA. Sildenafil reverses cardiac dysfunction in the mdx mouse model of Duchenne muscular dystrophy. Proc Natl Acad Sci USA 107: 19079-19083, 2010.
3. Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau-Ihling K, Zeiher AM, and Dimmeler S. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 9: 1370-1376, 2003.
4. Alderton WK, Cooper CE, and Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J 357: 593-615, 2001.
5. Alp NJ, Mussa S, Khoo J, Guzik TJ, Cai S, Jefferson A, Rockett KA, and Channon KM. Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I over-expression. J Clin Invest 112: 725-735, 2003.
6. Antoniades C, Demosthenous M, Reilly S, Margaritis M, Zhang MH, Antonopoulos A, Marinou K, Nahar K, Jayar-am R, Tousoulis D, Bakogiannis C, Sayeed R, Triantafyllou C, Koumallos N, Psarros C, Miliou A, Stefanadis C, Channon KM, and Casadei B. Myocardial redox state predicts in-hospital clinical outcome after cardiac surgery effects of short-term pre-operative statin treatment. J Am Coll Cardiol 59: 60-70, 2012.
7. Antoniades C, Shirodaria C, Leeson P, Antonopoulos A, Warrick N, Van-Assche T, Cunnington C, Tousoulis D, Pillai R, Ratnatunga C, Stefanadis C, and Channon KM. Association of plasma asymmetrical dimethylarginine (ADMA) with elevated vascular superoxide production and endothelial nitric oxide synthase uncoupling: implications for endothelial function in human atherosclerosis. Eur Heart J 30: 1142-1150, 2009.
8. Aragon JP, Condit ME, Bhushan S, Predmore BL, Patel SS, Grinsfelder DB, Gundewar S, Jha S, Calvert JW, Barouch LA, Lavu M, Wright HM, and Lefer DJ. Beta3-adrenoreceptor stimulation ameliorates myocardial ischemia-reperfusion injury via endothelial nitric oxide synthase and neuronal nitric oxide synthase activation. J Am Coll Cardiol 58: 2683-2691, 2011.
9. Arking DE, Pfeufer A, Post W, Kao WH, Newton-Cheh C, Ikeda M, West K, Kashuk C, Akyol M, Perz S, Jalilzadeh S, Illig T, Gieger C, Guo CY, Larson MG, Wichmann HE, Marban E, O'Donnell CJ, Hirschhorn JN, Kaab S, Spooner PM, Meitinger T, and Chakravarti A. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat Genet 38: 644-651, 2006.
10. Ashley EA, Sears CE, Bryant SM, Watkins HC, and Casadei B. Cardiac nitric oxide synthase 1 regulates basal and beta-adrenergic contractility in murine ventricular myocytes. Circulation 105: 3011-3016, 2002.
11. Bagnost T, Ma L, da Silva RF, Rezakhaniha R, Houdayer C, Stergiopulos N, Andre C, Guillaume Y, Berthelot A, and Demougeot C. Cardiovascular effects of arginase inhibition in spontaneously hypertensive rats with fully developed hypertension. Cardiovasc Res 87: 569-577, 2010.
12. Balafanova Z, Bolli R, Zhang J, Zheng Y, Pass JM, Bhat-nagar A, Tang XL, Wang O, Cardwell E, and Ping P. Nitric oxide (NO) induces nitration of protein kinase Cepsilon (PKCepsilon), facilitating PKCepsilon translocation via enhanced PKCepsilon-RACK2 interactions: a novel mechanism of no-triggered activation of PKCepsilon. J Biol Chem 277: 15021-15027, 2002.
13. Balligand JL, Kobzik L, Han X, Kaye DM, Belhassen L, O'Hara DS, Kelly RA, Smith TW, and Michel T. Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes. J Biol Chem 270: 14582-14586, 1995.
14. Barouch LA, Harrison RW, Skaf MW, Rosas GO, Cappola TP, Kobeissi ZA, Hobai IA, Lemmon CA, Burnett AL, O'Rourke B, Rodriguez ER, Huang PL, Lima JA, Berkowitz DE, and Hare JM. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 416: 337-339, 2002.
15. Beckman JS and Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271: C1424-1437, 1996.
16. Beigi F, Oskouei BN, Zheng M, Cooke CA, Lamirault G, and Hare JM. Cardiac nitric oxide synthase-1 localization within the cardiomyocyte is accompanied by the adaptor protein, CAPON. Nitric Oxide 21: 226-233, 2009.
17. Bencsik P, Kupai K, Giricz Z, Gorbe A, Huliak I, Furst S, Dux L, Csont T, Jancso G, and Ferdinandy P. Cardiac capsaicin-sensitive sensory nerves regulate myocardial relaxation via S-nitrosylation of SERCA: role of peroxynitrite. Br J Pharmacol 153: 488-496, 2008.
18. Bendall JK, Damy T, Ratajczak P, Loyer X, Monceau V, Marty I, Milliez P, Robidel E, Marotte F, Samuel J-L, and Heymes C. Role of myocardial neuronal nitric oxide syn-thase-derived nitric oxide in {beta}-adrenergic hypor-esponsiveness after myocardial infarction-induced heart failure in rat. Circulation 110: 2368-2375, 2004.
19. Berkowitz DE, White R, Li D, Minhas KM, Cernetich A, Kim S, Burke S, Shoukas AA, Nyhan D, Champion HC, and Hare JM. Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation 108: 2000-2006, 2003.
20. Bhatt SR, Lokhandwala MF, and Banday AA. Resveratrol prevents endothelial nitric oxide synthase uncoupling and attenuates development of hypertension in spontaneously hypertensive rats. Eur J Pharmacol 667: 258-264, 2011.
21. Biswas S, Chida AS, and Rahman I. Redox modifications of protein-thiols: emerging roles in cell signaling. Biochem Pharmacol 71: 551-564, 2006.
22. Brenman JE, Chao DS, Gee SH, Mcgee AW, Craven SE, Santillano DR, Wu ZQ, Huang F, Xia HH, Peters MF, Froehner SC, and Bredt DS. Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha-1-syntrophin mediated by PDZ domains. Cell 84: 757-767, 1996.
23. Brenman JE, Xia H, Chao DS, Black SM, and Bredt DS. Regulation of neuronal nitric oxide synthase through alternative transcripts. Dev Neurosci 19: 224-231, 1997.
24. Brixius K, Song Q, Malick A, Boelck B, Addicks K, Bloch W, Mehlhorn U, and Schwinger RH. ENOS is not activated by nebivolol in human failing myocardium. Life Sci 79: 1234-1241, 2006.
25. Burger DE, Lu X, Lei M, Xiang F-L, Hammoud L, Jiang M, Wang H, Jones DL, Sims SM, and Feng Q. Neuronal nitric oxide synthase protects against myocardial infarction-induced ventricular arrhythmia and mortality in mice. Circulation 120: 1345-1354, 2009.
26. Burgoyne JR, Madhani M, Cuello F, Charles RL, Brennan JP, Schroder E, Browning DD, and Eaton P. Cysteine redox sensor in PKGIa enables oxidant-induced activation. Science 317: 1393-1397, 2007.
27. Burkard N, Williams T, Czolbe M, Blomer N, Panther F, Link M, Fraccarollo D, Widder JD, Hu K, Han H, Hofmann U, Frantz S, Nordbeck P, Bulla J, Schuh K, and Ritter O. Conditional overexpression of neuronal nitric oxide syn-thase is cardioprotective in ischemia/reperfusion. Circulation 122: 1588-1603, 2010.
28. Buys ES, Raher MJ, Blake SL, Neilan TG, Graveline AR, Passeri JJ, Llano M, Perez-Sanz TM, Ichinose F, Janssens S, Zapol WM, Picard MH, Bloch KD, and Scherrer-Crosbie M. Cardiomyocyte-restricted restoration of nitric oxide syn-thase 3 attenuates left ventricular remodeling after chronic pressure overload. Am J Physiol Heart Circ Physiol 293: H620-H627, 2007.
29. Cai H, Li Z, Goette A, Mera F, Honeycutt C, Feterik K, Wilcox JN, Dudley SC, Jr., Harrison DG, and Langberg JJ. Downregulation of endocardial nitric oxide synthase expression and nitric oxide production in atrial fibrillation: potential mechanisms for atrial thrombosis and stroke. Circulation 106: 2854-2858, 2002.
30. Cai S, Khoo J, and Channon KM. Augmented BH4 by gene transfer restores nitric oxide synthase function in hyper-glycemic human endothelial cells. Cardiovasc Res 65: 823-831, 2005.
31. Campbell DL, Stamler JS, and Strauss HC. Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols. J Gen Physiol 108: 277-293, 1996.
32. Carnicer R, Hale AB, Liu X, Bendall JK, Lim GBS, Alp NJ, Channon KM, and Casadei B. Cardiomyocyte-targeted overexpression of GTP cyclohydrolase-1 increases nNOS activity and hastens myocardial relaxation. Eur Heart J 32: 154, 2011.
33. Chalupsky K and Cai H. Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase. Proc Natl Acad Sci USA 102: 9056-9061, 2005.
34. Chandra S, Romero MJ, Shatanawi A, Alkilany AM, Caldwell RB, and Caldwell RW. Oxidative species increase arginase activity in endothelial cells through the RhoA/Rho kinase pathway. Br J Pharmacol 165: 506-519, 2012.
35. Chang KC, Barth AS, Sasano T, Kizana E, Kashiwakura Y, Zhang Y, Foster DB, and Marban E. CAPON modulates cardiac repolarization via neuronal nitric oxide synthase signaling in the heart. Proc Natl Acad Sci USA 105: 4477-4482, 2008.
36. Cheang WS, Wong WT, Tian XY, Yang Q, Lee HK, He GW, Yao X, and Huang Y. Endothelial nitric oxide synthase enhancer reduces oxidative stress and restores endothelial function in db/db mice. Cardiovasc Res 92: 267-275, 2011.
37. Chen CA, Druhan LJ, Varadharaj S, Chen YR, and Zweier JL. Phosphorylation of endothelial nitric-oxide synthase regulates superoxide generation from the enzyme. J Biol Chem 283: 27038-27047, 2008.
38. Chen CA, Lin CH, Druhan LJ, Wang TY, Chen YR, and Zweier JL. Superoxide induces endothelial nitric-oxide synthase protein thiyl radical formation, a novel mechanism regulating eNOS function and coupling. J Biol Chem 286: 29098-29107, 2011.
39. Chen CA, Wang TY, Varadharaj S, Reyes LA, Hemann C, Talukder MA, Chen YR, Druhan LJ, and Zweier JL. S-glutathionylation uncouples eNOS and regulates its cellular and vascular function. Nature 468: 1115-1118, 2010.
40. Chen Z, Zhang J, and Stamler JS. Identification of the enzymatic mechanism of nitroglycerin bioactivation. Proc Natl Acad Sci USA 99: 8306-8311, 2002.
41. Chicoine LG, Paffett ML, Young TL, and Nelin LD. Argi-nase inhibition increases nitric oxide production in bovine pulmonary arterial endothelial cells. Am J Physiol Lung Cell Mol Physiol 287: L60-L68, 2004.
42. Cominacini L, Fratta Pasini A, Garbin U, Nava C, Davoli A, Criscuoli M, Crea A, Sawamura T, and Lo Cascio V. Ne-bivolol and its 4-keto derivative increase nitric oxide in endothelial cells by reducing its oxidative inactivation. J Am Coll Cardiol 42: 1838-1844, 2003.
43. Conraads VM, Metra M, Kamp O, De Keulenaer GW, Pieske B, Zamorano J, Vardas PE, Bohm M, and Dei Cas L. Effects of the long-term administration of nebivolol on the clinical symptoms, exercise capacity, and left ventricular function of patients with diastolic dysfunction: results of the ELANDD study. Eur J Heart Fail 14: 219-225, 2012.
44. Cooper AJ, Pinto JT, and Callery PS. Reversible and irreversible protein glutathionylation: biological and clinical aspects. Expert Opin Drug Metab Toxicol 7: 891-910, 2011.
45. Cotts WG and Johnson MR. The challenge of rejection and cardiac allograft vasculopathy. Heart Failure Rev 6: 227-240, 2001.
46. Crabtree MJ and Channon KM. Dihydrofolate reductase and biopterin recycling in cardiovascular disease. J Mol Cell Cardiol 47: 749-751, 2009.
47. Crabtree MJ, Hale AB, and Channon KM. Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency. Free Radic Biol Med 50: 1639-1646, 2011.
48. Crabtree MJ, Tatham AL, Al-Wakeel Y, Warrick N, Hale AB, Cai S, Channon KM, and Alp NJ. Quantitative regulation of intracellular endothelial nitric oxide synthase (eNOS) coupling by both tetrahydrobiopterin-eNOS stoi-chiometry and biopterin redox status: insights from cells with tet-regulated GTP cyclohydrolase I expression. J Biol Chem 284: 1136-1144, 2009.
49. Craig DH, Chapman SK, and Daff S. Calmodulin activates electron transfer through neuronal nitric-oxide synthase reductase domain by releasing an NADPH-dependent conformational lock. J Biol Chem 277: 33987-33994, 2002.
50. Daiber A, Oelze M, Coldewey M, Kaiser K, Huth C, Schildknecht S, Bachschmid M, Nazirisadeh Y, Ullrich V, Mulsch A, Munzel T, and Tsilimingas N. Hydralazine is a powerful inhibitor of peroxynitrite formation as a possible explanation for its beneficial effects on prognosis in patients with congestive heart failure. Biochem Biophys Res Commun 338: 1865-1874, 2005.
51. Damy T, Ratajczak P, Robidel E, Bendall JK, Oliviero P, Boczkowski J, Ebrahimian T, Marotte F, Samuel JL, and Heymes C. Up-regulation of cardiac nitric oxide synthase 1-derived nitric oxide after myocardial infarction in senescent rats. FASEB J 17: 1934-1936, 2003.
52. Damy T, Ratajczak P, Shah AM, Camors E, Marty I, Ha-senfuss G, Marotte F, Samuel JL, and Heymes C. Increased neuronal nitric oxide synthase-derived NO production in the failing human heart. Lancet 363: 1365-1367, 2004.
53. Danson EJ and Paterson DJ. Enhanced neuronal nitric oxide synthase expression is central to cardiac vagal phenotype in exercise-trained mice. J Physiol 546: 225-232, 2003.
54. Dawson D, Lygate CA, Zhang M-H, Hulbert K, Neubauer S, and Casadei B. nNOS gene deletion exacerbates pathological left ventricular remodeling and functional deterioration after myocardial infarction. Circulation 112: 3729-3737, 2005.
55. Demers P, Elkouri S, Sirois MG, and Cartier R. Coronary artery endothelial dysfunction after ischemia-reperfusion and acute untreated rejection in a canine heterotopic heart transplantation model. Transplantation 71: 26-32, 2001.
56. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, and Zeiher AM. Activation of nitric oxide synthase in en-dothelial cells by Akt-dependent phosphorylation. Nature 399: 601-605, 1999.
57. Doshi SN, Naka KK, Payne N, Jones CJ, Ashton M, Lewis MJ, and Goodfellow J. Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide. Clin Sci (Lond) 101: 629-635, 2001.
58. Drexler H, Kastner S, Strobel A, Studer R, Brodde OE, and Hasenfuss G. Expression, activity and functional significance of inducible nitric oxide synthase in the failing human heart. J Am Coll Cardiol 32: 955-963, 1998.
59. Duma D, Fernandes D, Bonini MG, Stadler K, Mason RP, and Assreuy J. NOS-1 derived NO is an essential triggering signal for the development of systemic inflammatory responses. Eur J Pharmacol 668: 285-292, 2011.
60. Dumitrescu C, Biondi R, Xia Y, Cardounel AJ, Druhan LJ, Ambrosio G, and Zweier JL. Myocardial ischemia results in tetrahydrobiopterin (BH4) oxidation with impaired endo-thelial function ameliorated by BH4. Proc Natl Acad Sci USA 104: 15081-15086, 2007.
61. Edes I, Gasior Z, and Wita K. Effects of nebivolol on left ventricular function in elderly patients with chronic heart failure: results of the ENECA study. Eur J Heart Failure 7: 631-639, 2005.
62. Eliasson MJ, Blackshaw S, Schell MJ, and Snyder SH. Neuronal nitric oxide synthase alternatively spliced forms: prominent functional localizations in the brain. Proc Natl Acad Sci USA 94: 3396-3401, 1997.
63. Eu JP, Xu L, Stamler JS, and Meissner G. Regulation of ryanodine receptors by reactive nitrogen species. Biochem Pharmacol 57: 1079-1084, 1999.
64. Feiner EC, Chung P, Jasmin JF, Zhang J, Whitaker-Menezes D, Myers V, Song J, Feldman EW, Funakoshi H, Degeorge BR, Jr., Yelamarty RV, Koch WJ, Lisanti MP, McTiernan CF, Cheung JY, Bristow MR, Chan TO, and Feldman AM. Left ventricular dysfunction in murine models of heart failure and in failing human heart is associated with a selective decrease in the expression of caveolin-3. J Card Fail 17: 253-263, 2011.
65. Feng Y, Venema VJ, Venema RC, Tsai N, and Caldwell RB. VEGF induces nuclear translocation of Flk-1/KDR, endothelial nitric oxide synthase, and caveolin-1 in vascular endothelial cells. Biochem Biophys Res Commun 256: 192-197, 1999.
66. Feron O, Belhassen L, Kobzik L, Smith TW, Kelly RA, and Michel T. Endothelial nitric oxide synthase targeting to caveolae. Specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J Biol Chem 271: 22810-22814, 1996.
67. Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, Cohen-Solal A, Dumitrascu D, Ferrari R, Lechat P, Soler-Soler J, Tavazzi L, Spinarova L, Toman J, Bohm M, Anker SD, Thompson SG, and Poole-Wilson PA. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 26: 215-225, 2005.
68. Fleming I and Busse R. Signal transduction of eNOS activation. Cardiovasc Res 43: 532-541, 1999.
69. Foster MW, Hess DT, and Stamler JS. Protein S-nitrosyla-tion in health and disease: a current perspective. Trends Mol Med 15: 391-404, 2009.
70. Francis SH, Busch JL, Corbin JD, and Sibley D. cGMP-dependent protein kinases and cGMP phosphodiester-ases in nitric oxide and cGMP action. Pharmacol Rev 62: 525-563, 2010.
71. Frey R, Muck W, Unger S, Artmeier-Brandt U, Weimann G, and Wensing G. Pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase activator cinaciguat (BAY 58-2667) in healthy male volunteers. J Clin Pharmacol 48: 1400-1410, 2008.
72. Fu JY, Qian LB, Zhu LG, Liang HT, Tan YN, Lu HT, Lu JF, Wang HP, and Xia Q. Betulinic acid ameliorates endothe-lium-dependent relaxation in L-NAME-induced hypertensive rats by reducing oxidative stress. Eur J Pharm Sci 44: 385-391, 2011.
73. Fulton D, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K, Franke TF, Papapetropoulos A, and Sessa WC. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 399: 597-601, 1999.
74. Fung HL and Bauer JA. Mechanisms of nitrate tolerance. Cardiovasc Drugs Ther 8: 489-499, 1994.
75. Gallis B, Corthals GL, Goodlett DR, Ueba H, Kim F, Pre-snell SR, Figeys D, Harrison DG, Berk BC, Aebersold R, and Corson MA. Identification of flow-dependent endothelial nitric-oxide synthase phosphorylation sites by mass spec-trometry and regulation of phosphorylation and nitric oxide production by the phosphatidylinositol 3-kinase inhibitor LY294002. J Biol Chem 274: 30101-30108, 1999.
76. Gao L, Pung YF, Zhang J, Chen P, Wang T, Li M, Meza M, Toro L, and Cai H. Sepiapterin reductase regulation of en-dothelial tetrahydrobiopterin and nitric oxide bioavailability. Am J Physiol Heart Circ Physiol 297: H331-H339, 2009.
77. Gauthier C, Leblais V, Kobzik L, Trochu JN, Khandoudi N, Bril A, Balligand JL, and Le Marec H. The negative ino-tropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle. J Clin Invest 102: 1377-1384, 1998.
78. Gazzerro E, Sotgia F, Bruno C, Lisanti MP, and Minetti C. Caveolinopathies: from the biology of caveolin-3 to human diseases. Eur J Hum Genet 18: 137-145, 2010.
79. Ghofrani HA, Hoeper MM, Halank M, Meyer FJ, Staehler G, Behr J, Ewert R, Weimann G, and Grimminger F. Rio-ciguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study. Eur Respir J 36: 792-799, 2010.
80. Godecke A, Heinicke T, Kamkin A, Kiseleva I, Strasser RH, Decking UK, Stumpe T, Isenberg G, and Schrader J. In-otropic response to beta-adrenergic receptor stimulation and anti-adrenergic effect of ACh in endothelial NO syn-thase-deficient mouse hearts. J Physiol 532: 195-204, 2001.
81. Gómez R, Caballero R, Barana A, Amorós I, Calvo E, López JA, Klein H, Vaquero M, Osuna L, Atienza F, Almendral J, Pinto A, Tamargo J, and Delpón E. Nitric oxide increases cardiac IK1 by nitrosylation of cysteine 76 of Kir2.1 channels. Circ Res 105: 383-392, 2009.
82. Gómez R, Núñez L, Vaquero M, Amorós I, Barana A, de Prada T, Macaya C, Maroto L, Rodŕiguez E, Caballero R, López-Farré A, Tamargo J, and Delpón E. Nitric oxide inhibits Kv4.3 and human cardiac transient outward potassium current (Ito1). Cardiovasc Res 80: 375-384, 2008.
83. Gonzalez DR, Beigi F, Treuer AV, and Hare JM. Deficient ryanodine receptor S-nitrosylation increases sarcoplasmic reticulum calcium leak and arrhythmogenesis in cardio-myocytes. Proc Natl Acad Sci USA 104: 20612-20617, 2007.
84. Gorren AC, List BM, Schrammel A, Pitters E, Hemmens B, Werner ER, Schmidt K, and Mayer B. Tetrahydrobiopterin-free neuronal nitric oxide synthase: evidence for two identical highly anticooperative pteridine binding sites. Biochemistry 35: 16735-16745, 1996.
85. Gross SS, Levi R, Madera A, Park KH, Vane J, and Hattori Y. Tetrahydrobiopterin synthesis is induced by LPS in vascular smooth muscle and is rate-limiting for nitric oxide production. Adv Exp Med Biol 338: 295-300, 1993.
86. Guazzi M, Casali M, Berti F, Rossoni G, Colonna VD, and Guazzi MD. Endothelium-mediated modulation of ergor-eflex and improvement in exercise ventilation by acute sildenafil in heart failure patients. Clin Pharmacol Ther 83: 336-341, 2008.
87. Guazzi M, Vicenzi M, Arena R, and Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail 4: 8-17, 2011.
88. Gyurko R, Kuhlencordt P, Fishman MC, and Huang PL. Modulation of mouse cardiac function in vivo by eNOS and ANP. Am J Physiol Heart Circ Physiol 278: H971-H981, 2000.
89. Hare JM. Nitroso-redox balance in the cardiovascular system. N Engl J Med 351: 2112-2114, 2004.
90. Hare JM, Mangal B, Brown J, Fisher C, Jr., Freudenberger R, Colucci WS, Mann DL, Liu P, Givertz MM, and Schwarz RP. Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF study. J Am Coll Cardiol 51: 2301-2309, 2008.
91. Hattori Y and Gross SS. GTP cyclohydrolase I mRNA is induced by LPS in vascular smooth muscle: characterization, sequence and relationship to nitric oxide synthase. Biochem Biophys Res Comm 195: 435-441, 1993.
92. Hattori Y, Nakanishi N, Akimoto K, Yoshida M, and Kasai K. HMG-CoA reductase inhibitor increases GTP cyclohy-drolase I mRNA and tetrahydrobiopterin in vascular endo-thelial cells. Arterioscler Thromb Vasc Biol 23: 176-182, 2003.
93. Hayashi Y, Nishio M, Naito Y, Yokokura H, Nimura Y, Hidaka H, and Watanabe Y. Regulation of neuronal nitric-oxide synthase by calmodulin kinases. J Biol Chem 274: 20597-20602, 1999.
94. Heitzer T, Schlinzig T, Krohn K, Meinertz T, and Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 104: 2673-2678, 2001.
95. Herring N and Paterson DJ. Neuromodulators of peripheral cardiac sympatho-vagal balance. Exp Physiol 94: 46-53, 2009.
96. Hess DT and Stamler JS. Regulation by S-nitrosylation of protein posttranslational modification. J Biol Chem 287: 4411-4418, 2012.
97. Hoke NN, Salloum FN, Kass DA, Das A, and Kukreja RC. Preconditioning by phosphodiesterase-5 inhibition improves therapeutic efficacy of adipose-derived stem cells following myocardial infarction in mice. Stem Cells 30: 326-335, 2012.
98. Horikawa YT, Panneerselvam M, Kawaraguchi Y, Tsutsu-mi YM, Ali SS, Balijepalli RC, Murray F, Head BP, Niesman IR, Rieg T, Vallon V, Insel PA, Patel HH, and Roth DM. Cardiac-specific overexpression of caveolin-3 attenuates cardiac hypertrophy and increases natriuretic peptide expression and signaling. J Am Coll Cardiol 57: 2273-2283, 2011.
99. Hurshman AR, Krebs C, Edmondson DE, Huynh BH, and Marletta MA. Formation of a pterin radical in the reaction of the heme domain of inducible nitric oxide synthase with oxygen. Biochemistry 38: 15689-15696, 1999.
100. Ignarro LJ. Different pharmacological properties of two enantiomers in a unique beta-blocker, nebivolol. Cardiovasc Ther 26: 115-134, 2008.
101. Ii M, Nishimura H, Iwakura A, Wecker A, Eaton E, Asa-hara T, and Losordo DW. Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via "imported" nitric oxide synthase activity. Circulation 111: 1114-1120, 2005.
102. Ionova IA, Vasquez-Vivar J, Whitsett J, Herrnreiter A, Medhora M, Cooley BC, and Pieper GM. Deficient BH4 production via de novo and salvage pathways regulates NO responses to cytokines in adult cardiac myocytes. Am J Physiol Heart Circ Physiol 295: H2178-H2187, 2008.
103. Iwakura A, Shastry S, Luedemann C, Hamada H, Kawamoto A, Kishore R, Zhu Y, Qin G, Silver M, Thorne T, Eaton L, Masuda H, Asahara T, and Losordo DW. Estradiol enhances recovery after myocardial infarction by augmenting incorporation of bone marrow-derived endothelial progenitor cells into sites of ischemia-induced neovascu-larization via endothelial nitric oxide synthase-mediated activation of matrix metalloproteinase-9. Circulation 113: 1605-1614, 2006.
104. Iwata A, Sai S, Nitta Y, Chen M, de Fries-Hallstrand R, Dalesandro J, Thomas R, and Allen MD. Liposome-mediated gene transfection of endothelial nitric oxide synthase reduces endothelial activation and leukocyte infiltration in transplanted hearts. Circulation 103: 2753-2759, 2001.
105. Janssens S, Pokreisz P, Schoonjans L, Pellens M, Ver-meersch P, Tjwa M, Jans P, Scherrer-Crosbie M, Picard MH, Szelid Z, Gillijns H, Van de Werf F, Collen D, and Bloch KD. Cardiomyocyte-specific overexpression of nitric oxide synthase 3 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. Circ Res 94: 1256-1262, 2004.
106. Jeppsson A, Pellegrini C, O'Brien T, Miller VM, Tazelaar HD, Taner CB, and McGregor CG. Gene transfer of endo-thelial nitric oxide synthase to pulmonary allografts: impact on acute rejection. Transpl Int 13 Suppl 1: S591-S596, 2000.
107. Jin CZ, Jang JH, Wang Y, Kim JG, Bae YM, Shi J, Che CR, Kim SJ, and Zhang YH. Neuronal nitric oxide synthase is up-regulated by angiotensin II and attenuates NADPH oxidase activity and facilitates relaxation in murine left ventricular myocytes. J Mol Cell Cardiol 52: 1274-1281, 2012.
108. Jones SP, Greer JJ, van Haperen R, Duncker DJ, de Crom R, and Lefer DJ. Endothelial nitric oxide synthase over-expression attenuates congestive heart failure in mice. Proc Natl Acad Sci USA 100: 4891-4896, 2003.
109. Jung C, Gonon AT, Sjoquist PO, Lundberg JO, and Pernow J. Arginase inhibition mediates cardioprotection during is-chaemia-reperfusion. Cardiovasc Res 85: 147-154, 2010.
110. Kao WH, Arking DE, Post W, Rea TD, Sotoodehnia N, Prineas RJ, Bishe B, Doan BQ, Boerwinkle E, Psaty BM, Tomaselli GF, Coresh J, Siscovick DS, Marban E, Spooner PM, Burke GL, and Chakravarti A. Genetic variations in nitric oxide synthase 1 adaptor protein are associated with sudden cardiac death in US white community-based populations. Circulation 119: 940-951, 2009.
111. Kar S and Kavdia M. Modeling of biopterin-dependent pathways of eNOS for nitric oxide and superoxide production. Free Radic Biol Med 51: 1411-1427, 2011.
112. Kawashima S, Yamashita T, Ozaki M, Ohashi Y, Azumi H, Inoue N, Hirata K-I, Hayashi Y, Itoh H, and Yokoyama M. Endothelial NO synthase overexpression inhibits lesion formation in mouse model of vascular remodeling. Arter-ioscler Thromb Vasc Biol 21: 201-207, 2001.
113. Kazakov A, Muller P, Jagoda P, Semenov A, Bohm M, and Laufs U. Endothelial nitric oxide synthase of the bone marrow regulates myocardial hypertrophy, fibrosis, and angiogenesis. Cardiovasc Res 93: 397-405, 2012.
114. Kelm M, Dahmann R, Wink D, and Feelisch M. The nitric oxide/superoxide assay. Insights into the biological chemistry of the NO/O-2. interaction. J Biol Chem 272: 9922-9932, 1997.
115. Khan SA, Lee K, Minhas KM, Gonzalez DR, Raju SV, Tejani AD, Li D, Berkowitz DE, and Hare JM. Neuronal nitric oxide synthase negatively regulates xanthine oxidoreduc-tase inhibition of cardiac excitation-contraction coupling. Proc Natl Acad Sci USA 101: 15944-15948, 2004.
116. Khong S, Andrews K, Huynh N, Venardos K, Aprico A, Michell D, Zarei M, Moe K, Dusting G, Kaye D, and Chin-Dusting J. Arginase II inhibition prevents nitrate tolerance. Br J Pharmacol 166: 2015-2023, 2012.
117. Kim D, Rybalkin SD, Pi X, Wang Y, Zhang C, Munzel T, Beavo JA, Berk BC, and Yan C. Upregulation of phos-phodiesterase 1A1 expression is associated with the development of nitrate tolerance. Circulation 104: 2338-2343, 2001.
118. Kim JH, Bugaj LJ, Oh YJ, Bivalacqua TJ, Ryoo S, Soucy KG, Santhanam L, Webb A, Camara A, Sikka G, Nyhan D, Shoukas AA, Ilies M, Christianson DW, Champion HC, and Berkowitz DE. Arginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats. J Appl Physiol 107: 1249-1257, 2009.
119. Kim YM, Guzik TJ, Zhang YH, Zhang MH, Kattach H, Ratnatunga C, Pillai R, Channon KM, and Casadei B. A myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative stress in human atrial fibrillation. Circ Res 97: 629-636, 2005.
120. Klinge CM, Wickramasinghe NS, Ivanova MM, and Dougherty SM. Resveratrol stimulates nitric oxide production by increasing estrogen receptor alpha-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells. FASEB J 22: 2185-2197, 2008.
121. Knowles RG and Moncada S. Nitric oxide synthases in mammals. Biochem J 298 (Pt 2): 249-258, 1994.
122. Knyushko T, Sharov VS, Williams TD, Shoneich C, and Bigelow DJ. 3-nitrotyrosine modification of SERCA2a in the aging heart: a distinct signature of the cellular redox environment. Biochemistry 44: 13071-13081, 2005.
123. Kobayashi YM, Rader EP, Crawford RW, Iyengar NK, Thedens DR, Faulkner JA, Parikh SV, Weiss RM, Chamberlain JS, Moore SA, and Campbell KP. Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature 456: 511-515, 2008.
124. Kohr MJ, Sun J, Aponte A, Wang G, Gucek M, Murphy E, and Steenbergen C. Simultaneous measurement of protein oxidation and S-nitrosylation during preconditioning and ischemia/reperfusion injury with resin-assisted capture. Circ Res 108: 418-426, 2011.
125. Koka S and Kukreja RC. Attenuation of doxorubicin-induced cardiotoxicity by tadalafil: a long acting phos-phodiesterase-5 inhibitor. Mol Cell Pharmacol 2: 173-178, 2010.
126. Kollau A, Beretta M, Russwurm M, Koesling D, Keung WM, Schmidt K, and Mayer B. Mitochondrial nitrite reduction coupled to soluble guanylate cyclase activation: lack of evidence for a role in the bioactivation of nitro-glycerin. Nitric Oxide 20: 53-60, 2009.
127. Kollau A, Hofer A, Russwurm M, Koesling D, Keung WM, Schmidt K, Brunner F, and Mayer B. Contribution of aldehyde dehydrogenase to mitochondrial bioactivation of nitroglycerin: evidence for the activation of purified soluble guanylate cyclase through direct formation of nitric oxide. Biochem J 385: 769-777, 2005.
128. Komeima K, Hayashi Y, Naito Y, and Watanabe Y. Inhibition of neuronal nitric-oxide synthase by calcium/calmodulin-dependent protein kinase IIalpha through Ser847 phosphorylation in NG108-15 neuronal cells. J Biol Chem 275: 28139-28143, 2000.
129. Kuhlencordt PJ, Hotten S, Schodel J, Rutzel S, Hu K, Widder J, Marx A, Huang PL, and Ertl G. Atheroprotective effects of neuronal nitric oxide synthase in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 26: 1539-1544, 2006.
130. Landmesser U, Engberding N, Bahlmann FH, Schaefer A, Wiencke A, Heineke A, Spiekermann S, Hilfiker-Kleiner D, Templin C, Kotlarz D, Mueller M, Fuchs M, Hornig B, Haller H, and Drexler H. Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neo-vascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation 110: 1933-1939, 2004.
131. Landmesser U, Spiekermann S, Dikalov S, Tatge H, Wilke R, Kohler C, Harrison DG, Hornig B, and Drexler H. Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: role of xanthine-oxidase and extracellular superoxide dismutase. Circulation 106: 3073-3078, 2002.
132. Laroux FS, Lefer DJ, Kawachi S, Scalia R, Cockrell AS, Gray L, Van der
133. Layland J, Li JM, and Shah AM. Role of cyclic GMP-dependent protein kinase in the contractile response to exogenous nitric oxide in rat cardiac myocytes. J Physiol 540: 457-467, 2002.
134. Lee DI, Vahebi S, Tocchetti CG, Barouch LA, Solaro RJ, Takimoto E, and Kass DA. PDE5A suppression of acute beta-adrenergic activation requires modulation of myocyte beta-3 signaling coupled to PKG-mediated troponin I phosphorylation. Basic Res Cardiol 105: 337-347, 2010.
135. Lefer DJ, Jones SP, Girod WG, Baines A, Grisham MB, Cockrell AS, Huang PL, and Scalia R. Leukocyte-endothe-lial cell interactions in nitric oxide synthase-deficient mice. Am J Physiol 276: H1943-H1950, 1999.
136. Leiper J, Nandi M, Torondel B, Murray-Rust J, Malaki M, O'Hara B, Rossiter S, Anthony S, Madhani M, Selwood D, Smith C, Wojciak-Stothard B, Rudiger A, Stidwill R, McDonald NQ, and Vallance P. Disruption of methylargi-nine metabolism impairs vascular homeostasis. Nat Med 13: 198-203, 2007.
137. Lewis NP, Tsao PS, Rickenbacher PR, Xue C, Johns RA, Haywood GA, von der Leyen H, Trindade PT, Cooke JP, Hunt SA, Billingham ME, Valantine HA, and Fowler MB. Induction of nitric oxide synthase in the human cardiac allograft is associated with contractile dysfunction of the left ventricle. Circulation 93: 720-729, 1996.
138. Li M, Chiou KR, Bugayenko A, Irani K, and Kass DA. Reduced wall compliance suppresses Akt-dependent apo-ptosis protection stimulated by pulse perfusion. Circ Res 97: 587-595, 2005.
139. Lima B, Lam GK, Xie L, Diesen DL, Villamizar N, Nienaber J, Messina E, Bowles D, Kontos CD, Hare JM, Stamler JS, and Rockman HA. Endogenous S-nitrosothiols protect against myocardial injury. Proc Natl Acad Sci USA 106: 6297-6302, 2009.
140. Lin MI, Fulton D, Babbitt R, Fleming I, Busse R, Pritchard KA, Jr., and Sessa WC. Phosphorylation of threonine 497 in endothelial nitric-oxide synthase coordinates the coupling of L-arginine metabolism to efficient nitric oxide production. J Biol Chem 278: 44719-44726, 2003.
141. Loke KE, McConnell PI, Tuzman JM, Shesely EG, Smith CJ, Stackpole CJ, Thompson CI, Kaley G, Wolin MS, and Hintze TH. Endogenous endothelial nitric oxide synthase-derived nitric oxide is a physiological regulator of myo-cardial oxygen consumption. Circ Res 84: 840-845, 1999.
142. Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, and Dagenais GR. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 293: 1338-1347, 2005.
143. Lorenz M, Hewing B, Hui J, Zepp A, Baumann G, Bindereif A, Stangl V, and Stangl K. Alternative splicing in intron 13 of the human eNOS gene: a potential mechanism for regulating eNOS activity. Faseb J 21: 1556-1564, 2007.
144. Luo Z, Fujio Y, Kureishi Y, Rudic RD, Daumerie G, Fulton D, Sessa WC, and Walsh K. Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent vasomotor activity in vivo. J Clin Invest 106: 493-499, 2000.
145. Maffei A, Di Pardo A, Carangi R, Carullo P, Poulet R, Gentile MT, Vecchione C, and Lembo G. Nebivolol induces nitric oxide release in the heart through inducible nitric oxide synthase activation. Hypertension 50: 652-656, 2007.
146. Martin SR, Emanuel K, Sears CE, Zhang YH, and Casadei B. Are myocardial eNOS and nNOS involved in the beta-adrenergic and muscarinic regulation of inotropy? a systematic investigation. Cardiovasc Res 70: 97-106, 2006.
147. Masters BS, McMillan K, Sheta EA, Nishimura JS, Roman LJ, and Martasek P. Neuronal nitric oxide synthase, a modular enzyme formed by convergent evolution: structure studies of a cysteine thiolate-liganded heme protein that hydroxylates L-arginine to produce NO. as a cellular signal [published erratum appears in FASEB J 10(9): 1107, 1996]. FASEB J 10: 552-558, 1996.
148. Matoba T, Shimokawa H, Nakashima M, Hirakawa Y, Mukai Y, Hirano K, Kanaide H, and Takeshita A. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. J Clin Invest 106: 1521-1530, 2000.
149. McEniery CM, Schmitt M, Qasem A, Webb DJ, Avolio AP, Wilkinson IB, and Cockcroft Jr. Nebivolol increases arterial distensibility in vivo. Hypertension 44: 305-310, 2004.
150. Michell BJ, Chen Z, Tiganis T, Stapleton D, Katsis F, Power DA, Sim AT, and Kemp BE. Coordinated control of endo-thelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem 276: 17625-17628, 2001.
151. Milstien S, Jaffe H, Kowlessur D, and Bonner TI. Purification and cloning of the GTP cyclohydrolase I feedback regulatory protein, GFRP. J Biol Chem 271: 19743-19751, 1996.
152. Minhas KM, Saraiva RM, Schuleri KH, Lehrke S, Zheng M, Saliaris AP, Berry CE, Barouch LA, Vandegaer KM, Li D, and Hare JM. Xanthine oxidoreductase inhibition causes reverse remodeling in rats with dilated cardiomyopathy. Circ Res 98: 271-279, 2006.
153. Moens AL, Ketner EA, Takimoto E, Schmidt TS, O'Neill CA, Wolin MS, Alp NJ, Channon KM, and Kass DA. Bi-modal dose-dependent cardiac response to tetra-hydrobiopterin in pressure-overload induced hypertrophy and heart failure. J Mol Cell Cardiol 51: 564-569, 2011.
154. Moens AL, Kietadisorn R, Lin JY, and Kass D. Targeting endothelial and myocardial dysfunction with tetra-hydrobiopterin. J Mol Cell Cardiol 51: 559-563, 2011.
155. Moens AL, Takimoto E, Tocchetti CG, Chakir K, Bedja D, Cormaci G, Ketner EA, Majmudar M, Gabrielson K, Halushka MK, Mitchell JB, Biswal S, Channon KM, Wolin MS, Alp NJ, Paolocci N, Champion HC, and Kass DA. Reversal of cardiac hypertrophy and fibrosis from pressure overload by tetrahydrobiopterin. Circulation 117: 2626-2636, 2008.
156. Moens AL, Vrints CJ, Claeys MJ, Timmermans JP, Champion HC, and Kass DA. Mechanisms and potential therapeutic targets for folic acid in cardiovascular disease. Am J Physiol Heart Circ Physiol 294: H1971-H1977, 2008.
157. Morikawa K, Shimokawa H, Matoba T, Kubota H, Akaike T, Talukder MA, Hatanaka M, Fujiki T, Maeda H, Taka-hashi S, and Takeshita A. Pivotal role of Cu, Zn-superoxide dismutase in endothelium-dependent hyperpolarization. J Clin Invest 112: 1871-1879, 2003.
158. Moroi M, Zhang L, Yasuda T, Virmani R, Gold HK, Fish-man MC, and Huang PL. Interaction of genetic deficiency of endothelial nitric oxide, gender, and pregnancy in vascular response to injury in mice. J Clin Invest 101: 1225-1232, 1998.
159. Munzel T, Kurz S, Rajagopalan S, Thoenes M, Berrington WR, Thompson JA, Freeman BA, and Harrison DG. Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase. A new action for an old drug. J Clin Invest 98: 1465-1470, 1996.
160. Nagayama T, Hsu S, Zhang M, Koitabashi N, Bedja D, Gabrielson KL, Takimoto E, and Kass DA. Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. J Am Coll Cardiol 53: 207-215, 2009.
161. Nakata S, Tsutsui M, Shimokawa H, Suda O, Morishita T, Shibata K, Yatera Y, Sabanai K, Tanimoto A, Nagasaki M, Tasaki H, Sasaguri Y, Nakashima Y, Otsuji Y, and Yana-gihara N. Spontaneous myocardial infarction in mice lacking all nitric oxide synthase isoforms. Circulation 117: 2211-2223, 2008.
162. Nasr G and Maurice C. Allopurinol and global left myo-cardial function in heart failure patients. J Cardiovasc Dis Res 1: 191-195, 2010.
163. Nichol CA, Lee CL, Edelstein MP, Chao JY, and Duch DS. Biosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mammalian cell cultures, and rat brain in vivo. Proc Natl Acad Sci USA 80: 1546-1550, 1983.
164. Nunez L, Vaquero M, Gomez R, Caballero R, Mateos-Caceres P, Macaya C, Iriepa I, Galvez E, Lopez-Farre A, Tamargo J, and Delpon E. Nitric oxide blocks hKv1.5 channels by S-nitrosylation and by a cyclic GMP-dependent mechanism. Cardiovasc Res 72: 80-89, 2006.
165. Oceandy D, Cartwright EJ, Emerson M, Prehar S, Baudoin FM, Zi M, Alatwi N, Venetucci L, Schuh K, Williams JC, Armesilla AL, and Neyses L. Neuronal nitric oxide synthase signaling in the heart is regulated by the sarcolemmal calcium pump 4b. Circulation 115: 483-492, 2007.
166. Oelze M, Daiber A, Brandes RP, Hortmann M, Wenzel P, Hink U, Schulz E, Mollnau H, von Sandersleben A, Kle-schyov AL, Mulsch A, Li H, Forstermann U, and Munzel T. Nebivolol inhibits superoxide formation by NADPH oxi-dase and endothelial dysfunction in angiotensin II-treated rats. Hypertension 48: 677-684, 2006.
167. Otani H. The role of nitric oxide in myocardial repair and remodeling. Antioxid Redox Signal 11: 1913-1928, 2009.
168. Ozawa K, Whalen EJ, Nelson CD, Mu Y, Hess DT, Lefko-witz RJ, and Stamler JS. S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor trafficking. Mol cell 31: 395-405, 2008.
169. Parenti A, Filippi S, Amerini S, Granger HJ, Fazzini A, and Ledda F. Inositol phosphate metabolism and nitric-oxide synthase activity in endothelial cells are involved in the vasorelaxant activity of nebivolol. J Pharmacol Exp Ther 292: 698-703, 2000.
170. Paulus WJ, Vantrimpont PJ, and Shah AM. Paracrine coronary endothelial control of left ventricular function in humans. Circulation 92: 2119-2126, 1995.
171. Pearson JD. Endothelial progenitor cells-an evolving story. Microvasc Res 79: 162-168, 2010.
172. Percival JM, Anderson KN, Huang P, Adams ME, and Froehner SC. Golgi and sarcolemmal neuronal NOS differentially regulate contraction-induced fatigue and vaso-constriction in exercising mouse skeletal muscle. J Clin Invest 120: 816-826, 2010.
173. Perrault LP, Bidouard JP, Janiak P, Villeneuve N, Bruneval P, Vilaine JP, and Vanhoutte PM. Time course of coronary endothelial dysfunction in acute untreated rejection after heterotopic heart transplantation. J Heart Lung Transplant 16: 643-657, 1997.
174. Petroff MG, Kim SH, Pepe S, Dessy C, Marban E, Balligand JL, and Sollott SJ. Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release in cardi-omyocytes. Nat Cell Biol 3: 867-873, 2001.
175. Piech A, Massart PE, Dessy C, Feron O, Havaux X, Morel N, Vanoverschelde JL, Donckier J, and Balligand JL. Decreased expression of myocardial eNOS and caveolin in dogs with hypertrophic cardiomyopathy. Am J Physiol Heart Circ Physiol 282: H219-H231, 2002.
176. Pinsky DJ, Patton S, Mesaros S, Brovkovych V, Ku-baszewski E, Grunfeld S, and Malinski T. Mechanical transduction of nitric oxide synthesis in the beating heart. Circ Res 81: 372-379, 1997.
177. Predmore BL, Julian D, and Cardounel AJ. Hydrogen sul-fide increases nitric oxide production from endothelial cells by an akt-dependent mechanism. Front Physiol 2: 104, 2011.
178. Prendergast BD, Sagach VF, and Shah AM. Basal release of nitric oxide augments the Frank-Starling response in the isolated heart. Circulation 96: 1320-1329, 1997.
179. Prysyazhna O, Rudyk O, and Eaton P. Single atom substitution in mouse protein kinase G eliminates oxidant sensing to cause hypertension. Nat Med 18: 286-290, 2012.
180. Rakhit A, Maguire CT, Wakimoto H, Gehrmann J, Li GK, Kelly RA, Michel T, and Berul CI. In vivo electrophysio-logic studies in endothelial nitric oxide synthase (eNOS)-deficient mice. J Cardiovasc Electrophysiol 12: 1295-1301, 2001.
181. Raman CS, Li H, Martasek P, Kral V, Masters BS, and Poulos TL. Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center. Cell 95: 939-950, 1998.
182. Rameau GA, Chiu LY, and Ziff EB. Bidirectional regulation of neuronal nitric-oxide synthase phosphorylation at serine 847 by the N-methyl-D-aspartate receptor. J Biol Chem 279: 14307-14314, 2004.
183. Reilly SN, Jayaram R, Nahar K, Antoniades C, Verheule S, Channon KM, Alp NJ, Schotten U, and Casadei B. Atrial sources of reactive oxygen species vary with the duration and substrate of atrial fibrillation: implications for the an-tiarrhythmic effect of statins. Circulation 124: 1107-1117, 2011.
184. Ren J, Duan J, Thomas DP, Yang X, Sreejayan N, Sowers JR, Leri A, Kajstura J, Gao F, and Anversa P. IGF-I alleviates diabetes-induced RhoA activation, eNOS uncoupling, and myocardial dysfunction. Am J Physiol Regul Integr Comp Physiol 294: R793-R802, 2008.
185. Rodriguez-Crespo I, Gerber NC, and Ortiz de Montellano PR. Endothelial nitric-oxide synthase. Expression in Es-cherichia coli, spectroscopic characterization, and role of tetrahydrobiopterin in dimer formation. J Biol Chem 271: 11462-11467, 1996.
186. Rozec B and Gauthier C. Beta3-adrenoceptors in the cardiovascular system: putative roles in human pathologies. Pharmacol Ther 111: 652-673, 2006.
187. Ruetten H, Dimmeler S, Gehring D, Ihling C, and Zeiher AM. Concentric left ventricular remodeling in endothelial nitric oxide synthase knockout mice by chronic pressure overload. Cardiovasc Res 66: 444-453, 2005.
188. Saavedra WF, Paolocci N, St John ME, Skaf MW, Stewart GC, Xie JS, Harrison RW, Zeichner J, Mudrick D, Marban E, Kass DA, and Hare JM. Imbalance between xanthine oxi-dase and nitric oxide synthase signaling pathways underlies mechanoenergetic uncoupling in the failing heart. Circ Res 90: 297-304, 2002.
189. Saeki A, Recchia FA, Senzaki H, and Kass DA. Minimal role of nitric oxide in basal coronary flow regulation and cardiac energetics of blood-perfused isolated canine heart. J Physiol 491 (Pt 2): 455-463, 1996.
190. Salloum F, Yin C, Xi L, and Kukreja RC. Sildenafil induces delayed preconditioning through inducible nitric oxide synthase-dependent pathway in mouse heart. Circ Res 92: 595-597, 2003.
191. Salloum FN, Abbate A, Das A, Houser JE, Mudrick CA, Qureshi IZ, Hoke NN, Roy SK, Brown WR, Prabhakar S, and Kukreja RC. Sildenafil (Viagra) attenuates ischemic cardiomyopathy and improves left ventricular function in mice. Am J Physiol Heart Circ Physiol 294: H1398-H1406, 2008.
192. Santhanam L, Christianson DW, Nyhan D, and Berkowitz DE. Arginase and vascular aging. J Appl Physiol 105: 1632-1642, 2008.
193. Saraiva RM, Minhas KM, Raju SV, Barouch LA, Pitz E, Schuleri KH, Vandegaer K, Li D, and Hare JM. Deficiency of neuronal nitric oxide synthase increases mortality and cardiac remodeling after myocardial infarction: role of nitroso-redox equilibrium. Circulation 112: 3415-3422, 2005.
194. Sartoretto JL, Kalwa H, Pluth MD, Lippard SJ, and Michel T. Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis. Proc Natl Acad Sci USA 108: 15792-15797, 2011.
195. Scherrer-Crosbie M, Ullrich R, Bloch KD, Nakajima H, Nasseri B, Aretz HT, Lindsey ML, Vancon AC, Huang PL, Lee RT, Zapol WM, and Picard MH. Endothelial nitric oxide synthase limits left ventricular remodeling after myocardial infarction in mice. Circulation 104: 1286-1291, 2001.
196. Schmidt PP, Lange R, Gorren AC, Werner ER, Mayer B, and Andersson KK. Formation of a protonated trihy-drobiopterin radical cation in the first reaction cycle of neuronal and endothelial nitric oxide synthase detected by electron paramagnetic resonance spectroscopy. J Biol Inorg Chem 6: 151-158, 2001.
197. Sears CE, Bryant SM, Ashley EA, Lygate CA, Rakovic S, Wallis HL, Neubauer S, Terrar DA, and Casadei B. Cardiac neuronal nitric oxide synthase isoform regulates myocar-dial contraction and calcium handling. Circ Res 92: e52-e59, 2003.
198. Seddon M, Melikian N, Dworakowski R, Shabeeh H, Jiang B, Byrne J, Casadei B, Chowienczyk P, and Shah AM. Effects of neuronal nitric oxide synthase on human coronary artery diameter and blood flow in vivo. Circulation 119: 2656-2662, 2009.
199. Seddon MD, Chowienczyk PJ, Brett SE, Casadei B, and Shah AM. Neuronal nitric oxide synthase regulates basal microvascular tone in humans in vivo. Circulation 117: 1991-1996, 2008.
200. Sharma NM, Zheng H, Mehta PP, Li Y-F, and Patel KP. Decreased nNOS in the PVN leads to increased sym-pathoexcitation in chronic heart failure: role for CAPON and Ang II. Cardiovasc Res 92: 348-357, 2011.
201. Shimazu T, Otani H, Yoshioka K, Fujita M, Okazaki T, and Iwasaka T. Sepiapterin enhances angiogenesis and functional recovery in mice after myocardial infarction. Am J Physiol Heart Circ Physiol 301: H2061-H2072, 2011.
202. Shimizu S, Shiota K, Yamamoto S, Miyasaka Y, Ishii M, Watabe T, Nishida M, Mori Y, Yamamoto T, and Kiuchi Y. Hydrogen peroxide stimulates tetrahydrobiopterin synthesis through the induction of GTP-cyclohydrolase I and increases nitric oxide synthase activity in vascular endo-thelial cells. Free Radic Biol Med 34: 1343-1352, 2003.
203. Shimokawa H and Morikawa K. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in animals and humans. J Mol Cell Cardiol 39: 725-732, 2005.
204. Silberman GA, Fan TH, Liu H, Jiao Z, Xiao HD, Lovelock JD, Boulden BM, Widder J, Fredd S, Bernstein KE, Wolska BM, Dikalov S, Harrison DG, and Dudley SC, Jr. Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction. Circulation 121: 519-528, 2010.
205. Sorrentino SA, Doerries C, Manes C, Speer T, Dessy C, Lobysheva I, Mohmand W, Akbar R, Bahlmann F, Besler C, Schaefer A, Hilfiker-Kleiner D, Luscher TF, Balligand JL, Drexler H, and Landmesser U. Nebivolol exerts beneficial effects on endothelial function, early endothelial progenitor cells, myocardial neovascularization, and left ventricular dysfunction early after myocardial infarction beyond conventional beta1-blockade. J Am Coll Cardiol 57: 601-611, 2011.
206. Stadler K, Bonini MG, Dallas S, Duma D, Mason RP, and Kadiiska MB. Direct evidence of iNOS-mediated in vivo free radical production and protein oxidation in acetone-induced ketosis. Am J Physiol Endocrinol Metab 295: E456-E462, 2008.
207. Steinkamp-Fenske K, Bollinger L, Xu H, Yao Y, Horke S, Forstermann U, and Li H. Reciprocal regulation of endo-thelial nitric-oxide synthase and NADPH oxidase by be-tulinic acid in human endothelial cells. J Pharmacol Exp Ther 322: 836-842, 2007.
208. Steppan J, Ryoo S, Schuleri KH, Gregg C, Hasan RK, White AR, Bugaj LJ, Khan M, Santhanam L, Nyhan D, Shoukas AA, Hare JM, and Berkowitz DE. Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism. Proc Natl Acad Sci USA 103: 4759-4764, 2006.
209. Stuehr DJ. Mammalian nitric oxide synthases. Biochim Bio-phys Acta 1411: 217-230, 1999.
210. Sugiyama T, Levy BD, and Michel T. Tetrahydrobiopterin recycling, a key determinant of endothelial nitric-oxide synthase-dependent signaling pathways in cultured vascular endothelial cells. J Biol Chem 284: 12691-12700, 2009.
211. Sun J, Druhan LJ, and Zweier JL. Dose dependent effects of reactive oxygen and nitrogen species on the function of neuronal nitric oxide synthase. Arch Biochem Biophys 471: 126-133, 2008.
212. Sun J, Picht E, Ginsburg KS, Bers DM, Steenbergen C, and Murphy E. Hypercontractile female hearts exhibit increased S-nitrosylation of the L-type Ca2+ channel alpha1 subunit and reduced ischemia/reperfusion injury. Circ Res 98: 403-411, 2006.
213. Szabolcs MJ, Ma N, Athan E, Zhong J, Ming M, Sciacca RR, Husemann J, Albala A, and Cannon PJ. Acute cardiac al-lograft rejection in nitric oxide synthase-2(-/-) and nitric oxide synthase-2 (+/+) mice: effects of cellular chimeras on myocardial inflammation and cardiomyocyte damage and apoptosis. Circulation 103: 2514-2520, 2001.
214. Szocs K, Lassegue B, Wenzel P, Wendt M, Daiber A, Oelze M, Meinertz T, Munzel T, and Baldus S. Increased super-oxide production in nitrate tolerance is associated with NAD(P)H oxidase and aldehyde dehydrogenase 2 down-regulation. J Mol Cell Cardiol 42: 1111-1118, 2007.
215. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y, and Kass DA. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 11: 214-222, 2005.
216. Takimoto E, Champion HC, Li M, Ren S, Rodriguez ER, Tavazzi B, Lazzarino G, Paolocci N, Gabrielson KL, Wang Y, and Kass DA. Oxidant stress from nitric oxide synthase-3 uncoupling stimulates cardiac pathologic remodeling from chronic pressure load. J Clin Invest 115: 1221-1231, 2005.
217. Takimoto Y, Aoyama T, Tanaka K, Keyamura R, Yui Y, and Sasayama S. Augmented expression of neuronal nitric oxide synthase in the atria parasympathetically decreases heart rate during acute myocardial infarction in rats. Circulation 105: 490-496, 2002.
218. Tatsumi T, Matoba S, Kawahara A, Keira N, Shiraishi J, Akashi K, Kobara M, Tanaka T, Katamura M, Nakagawa C, Ohta B, Shirayama T, Takeda K, Asayama J, Fliss H, and Nakagawa M. Cytokine-induced nitric oxide production inhibits mitochondrial energy production and impairs contractile function in rat cardiac myocytes. J Am Coll Cardiol 35: 1338-1346, 2000.
219. Taylor AL, Ziesche S, Yancy C, Carson P, D'Agostino R, Jr., Ferdinand K, Taylor M, Adams K, Sabolinski M, Worcel M, and Cohn JN. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 351: 2049-2057, 2004.
220. Thoenes M, Forstermann U, Tracey WR, Bleese NM, Nussler AK, Scholz H, and Stein B. Expression of inducible nitric oxide synthase in failing and non-failing human heart. J Mol Cell Cardiol 28: 165-169, 1996.
221. Thony B, Auerbach G, and Blau N. Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochem J 347: 1-16, 2000.
222. Torfgard KE and Ahlner J. Mechanisms of action of nitrates. Cardiovasc Drugs Ther 8: 701-717, 1994.
223. Traverso M, Gazzerro E, Assereto S, Sotgia F, Biancheri R, Stringara S, Giberti L, Pedemonte M, Wang X, Scapolan S, Pasquini E, Donati MA, Zara F, Lisanti MP, Bruno C, and Minetti C. Caveolin-3 T78M and T78K missense mutations lead to different phenotypes in vivo and in vitro. Lab Invest J Tech Methods Pathol 88: 275-283, 2008.
224. Tsai EJ, Liu Y, Koitabashi N, Bedja D, Danner T, Jasmin JF, Lisanti MP, Friebe A, Takimoto E, and Kass DA. Pressure-overload-induced subcellular relocalization/oxidation of soluble guanylyl cyclase in the heart modulates enzyme stimulation. Circ Res 110: 295-303, 2012.
225. Tsujita Y, Muraski J, Shiraishi I, Kato T, Kajstura J, Anversa P, and Sussman MA. Nuclear targeting of Akt antagonizes aspects of cardiomyocyte hypertrophy. Proc Natl Acad Sci USA 103: 11946-11951, 2006.
226. Tsutsui M, Nakata S, Shimokawa H, Otsuji Y, and Yana-gihara N. Spontaneous myocardial infarction and nitric oxide synthase. Trends Cardiovasc Med 18: 275-279, 2008.
227. Tziomalos K and Hare JM. Role of xanthine oxidoreductase in cardiac nitroso-redox imbalance. Front Biosci J Virtual Libr 14: 237-262, 2009.
228. Ueda K, Valdivia C, Medeiros-Domingo A, Tester DJ, Vatta M, Farrugia G, Ackerman MJ, and Makielski JC. Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromo-lecular complex. Proc Natl Acad Sci USA 105: 9355-9360, 2008.
229. van Haperen R, de Waard M, van Deel E, Mees B, Kutryk M, van Aken T, Hamming J, Grosveld F, Duncker DJ, and de Crom R. Reduction of blood pressure, plasma cholesterol, and atherosclerosis by elevated endothelial nitric oxide. J Biol Chem 277: 48803-48807, 2002.
230. Vandecasteele G, Eschenhagen T, Scholz H, Stein B, Verde I, and Fischmeister R. Muscarinic and beta-adrenergic regulation of heart rate, force of contraction and calcium current is preserved in mice lacking endothelial nitric oxide synthase. Nat Med 5: 331-334, 1999.
231. Vasquez-Vivar J, Duquaine D, Whitsett J, Kalyanaraman B, and Rajagopalan S. Altered tetrahydrobiopterin metabolism in atherosclerosis: implications for use of oxidized tetrahydrobiopterin analogues and thiol antioxidants. Ar-terioscler Thromb Vasc Biol 22: 1655-1661, 2002.
232. Vasquez-Vivar J, Hogg N, Martasek P, Karoui H, Pritchard KA, Jr., and Kalyanaraman B. Tetrahydrobiopterin-dependent inhibition of superoxide generation from neu-ronal nitric oxide synthase. J Biol Chem 274: 26736-26742, 1999.
233. Vasquez-Vivar J, Kalyanaraman B, and Martasek P. The role of tetrahydrobiopterin in superoxide generation from eNOS: enzymology and physiological implications. Free Radic Res 37: 121-127, 2003.
234. Vasquez-Vivar J, Martasek P, Whitsett J, Joseph J, and Kalyanaraman B. The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls su-peroxide release from endothelial nitric oxide synthase: an EPR spin trapping study. Biochem J 362: 733-739, 2002.
235. Visser M, Paulus WJ, Vermeulen MA, Richir MC, Davids M, Wisselink W, de Mol BA, and van Leeuwen PA. The role of asymmetric dimethylarginine and arginine in the failing heart and its vasculature. Eur J Heart Fail 12: 1274-1281, 2010.
236. Vo PA, Lad B, Tomlinson JA, Francis S, and Ahluwalia A. Autoregulatory role of endothelium-derived nitric oxide (NO) on lipopolysaccharide-induced vascular inducible NO synthase expression and function. J Biol Chem 280: 7236-7243, 2005.
237. Vogel MW and Chen HH. Novel natriuretic peptides: new compounds and new approaches. Curr Heart Fail Rep 8: 22-27, 2011.
238. Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, and Forstermann U. Resveratrol, a polyphenolic phyto-alexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 106: 1652-1658, 2002.
239. Wang H, Kohr MJ, Traynham CJ, Wheeler DG, Janssen PM, and Ziolo MT. Neuronal nitric oxide synthase signaling within cardiac myocytes targets phospholamban. Am J Physiol Cell Physiol 294: C1566-C1575, 2008.
240. Wang H, Kohr MJ, Traynham CJ, and Ziolo MT. Phos-phodiesterase 5 restricts NOS3/soluble guanylate cyclase signaling to L-type Ca2 + current in cardiac myocytes. J Mol Cell Cardiol 47: 304-314, 2009.
241. Wang H, Kohr MJ, Wheeler DG, and Ziolo MT. Endothelial nitric oxide synthase decreases beta-adrenergic responsiveness via inhibition of the L-type Ca2+ current. Am J Physiol Heart Circ Physiol 294: H1473-H1480, 2008.
242. Wang H, Viatchenko-Karpinski S, Sun J, Gyorke I, Ben-kusky NA, Kohr MJ, Valdivia HH, Murphy E, Gyorke S, and Ziolo MT. Regulation of myocyte contraction via neuronal nitric oxide synthase: role of ryanodine receptor S-nitrosylation. J Physiol 588: 2905-2917, 2010.
243. West MB, Rokosh G, Obal D, Velayutham M, Xuan YT, Hill BG, Keith RJ, Schrader J, Guo Y, Conklin DJ, Prabhu SD, Zweier JL, Bolli R, and Bhatnagar A. Cardiac myocyte-specific expression of inducible nitric oxide synthase protects against ischemia/reperfusion injury by preventing mitochondrial permeability transition. Circulation 118: 1970-1978, 2008.
244. Whalen EJ, Foster MW, Matsumoto A, Ozawa K, Violin JD, Que LG, Nelson CD, Benhar M, Keys JR, Rockman HA, Koch WJ, Daaka Y, Lefkowitz RJ, and Stamler JS. Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2. Cell 129: 511-522, 2007.
245. Whiteman M, Le Trionnaire S, Chopra M, Fox B, and Whatmore J. Emerging role of hydrogen sulfide in health and disease: critical appraisal of biomarkers and pharmacological tools. Clin Sci (Lond) 121: 459-488, 2011.
246. Widder JD, Chen W, Li L, Dikalov S, Thony B, Hatakeyama K, and Harrison DG. Regulation of tetrahydrobiopterin biosynthesis by shear stress. Circ Res 101: 830-838, 2007.
247. Wilcox JN, Subramanian RR, Sundell CL, Tracey WR, Pollock JS, Harrison DG, and Marsden PA. Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels. Arterioscler Thromb Vasc Biol 17: 2479-2488, 1997.
248. Wolfhart P, Xu H, Endlich A, Habermeier A, Closs EI, Hubschle T, Mang C, Strobel H, Suzuki T, Kleinert H, Förstermann U, Ruetten H, and Li H. Antiatherosclerotic effects of small-molecular-weight compounds enhancing endothelial nitric-oxide synthase (eNOS) expression and preventing eNOS uncoupling. J Pharmocol Exp Ther 325: 370-379, 2008.
249. Woodman SE, Park DS, Cohen AW, Cheung MW, Chandra M, Shirani J, Tang B, Jelicks LA, Kitsis RN, Christ GJ, Factor SM, Tanowitz HB, and Lisanti MP. Caveolin-3 knock-out mice develop a progressive cardiomyopathy and show hyperactivation of the p42/44 MAPK cascade. J Biol Chem 277: 38988-38997, 2002.
250. Xia N, Daiber A, Habermeier A, Closs EI, Thum T, Spanier G, Lu Q, Oelze M, Torzewski M, Lackner KJ, Munzel T, Forstermann U, and Li H. Resveratrol reverses endothelial nitric-oxide synthase uncoupling in apolipoprotein E knockout mice. J Pharmacol Exp Ther 335: 149-154, 2010.
251. Xie YW and Wolin MS. Role of nitric oxide and its interaction with superoxide in the suppression of cardiac muscle mitochondrial respiration. Involvement in response to hypoxia/reoxygenation. Circulation 94: 2580-2586, 1996.
252. Xu KY, Huso DL, Dawson TM, Bredt DS, and Becker LC. Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci USA 96: 657-662, 1999.
253. Xu Z, Ji X, and Boysen PG. Exogenous nitric oxide generates ROS and induces cardioprotection: involvement of PKG, mitochondrial KATP channels, and ERK. Am J Physiol Heart Circ Physiol 286: H1433-H1440, 2004.
254. Yang L, Liu G, Zakharov SI, Bellinger AM, Mongillo M, and Marx SO. Protein kinase G phosphorylates Cav1.2 al-pha1c and beta2 subunits. Circ Res 101: 465-474, 2007.
255. Yap J, O'Brien T, Pellegrini C, Barber DA, Tazelaar HD, Severson SR, Miller VM, and McGregor CG. Distribution and function of recombinant endothelial nitric oxide syn-thase in transplanted hearts. Cardiovasc Res 42: 720-727, 1999.
256. Yogo K, Shimokawa H, Funakoshi H, Kandabashi T, Miyata K, Okamoto S, Egashira K, Huang P, Akaike T, and Takeshita A. Different vasculoprotective roles of NO syn-thase isoforms in vascular lesion formation in mice. Arter-ioscler Thromb Vasc Biol 20: E96-E100, 2000.
257. Yoneyama T, Brewer JM, and Hatakeyama K. GTP cyclo-hydrolase I feedback regulatory protein is a pentamer of identical subunits. Purification, cDNA cloning, and bacterial expression. J Biol Chem 272: 9690-9696, 1997.
258. Zhang K, Mayhan WG, and Patel KP. Nitric oxide within the paraventricular nucleus mediates changes in renal sympathetic nerve activity. Am J Physiol 273: R864-R872, 1997.
259. Zhang YH, Zhang MH, Sears CE, Emanuel K, Redwood C, El-Armouche A, Kranias EG, and Casadei B. Reduced phospholamban phosphorylation is associated with impaired relaxation in left ventricular myocytes from neuro-nal NO synthase-deficient mice. Circ Res 102: 242-249, 2008.
260. Zhao X, Lu X, and Feng Q. Deficiency in endothelial nitric oxide synthase impairs myocardial angiogenesis. Am J Physiol Heart Circ Physiol 283: H2371-H2378, 2002.
261. Zou MH, Shi C, and Cohen RA. Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite. J Clin Invest 109: 817-826, 2002.