Role of nitric oxide in the pathophysiology of heart failure

Heart Failure Reviews

Volumn 8, Issue 1, 2003, Pages 35-46

  Champion, Hunter C ^a   Skaf, Michel W ^a   Hare, Joshua M ^a  

^a JOHNS HOPKINS HOSPITAL   (United States)

Author keywords

Heart failure; Myocyte; Nitric oxide; Spatial compartmentalization

Indexed keywords

ALLOPURINOL; ARGININE; BETA 1 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR; BETA 3 ADRENERGIC RECEPTOR; CAVEOLIN 3; CYCLIC GMP; N(G) METHYLARGININE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE INHIBITOR; NITROPRUSSIDE SODIUM; PHOSPHODIESTERASE; PHOSPHODIESTERASE INHIBITOR; PHOSPHODIESTERASE V; REACTIVE NITROGEN SPECIES; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

CORONARY ARTERY DILATATION; CORONARY HEMODYNAMICS; DIASTOLIC BLOOD PRESSURE; DRUG EFFECT; ENZYME ACTIVITY; HEART FAILURE; HEART FUNCTION; HEART HYPERTROPHY; HEART LEFT VENTRICLE RELAXATION; HEART MITOCHONDRION; HEART MUSCLE CELL; HOMEOSTASIS; HUMAN; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SYSTOLIC BLOOD PRESSURE; VASCULAR ENDOTHELIUM; VASCULARIZATION;

ENDOTHELIUM, VASCULAR; HEART FAILURE, CONGESTIVE; HUMANS; MYOCYTES, CARDIAC; NITRIC OXIDE; SIGNAL TRANSDUCTION;

EID: 0037230897     PISSN: 13824147     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1022142904202     Document Type: Review

References (126)

1. Stamler JS, Lamas S, Fang FC. Nitrosylation. The prototypic redox-based signaling mechanism. Cell 2001;106:675-683.
2. Hare JM, Stamler JS. NOS: Modulator, not mediator of cardiac performance. Nat Med 1999;5:273-274.
3. 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, Hare JM. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 2002;416:337-339.
4. Michel T, Feron O. Nitric oxide synthases: Which, where, how and why? J Clin Invest 1997;100:2146-2152.
5. Bates TE, Loesch A, Burnstock G, Clark JB. Mitochondrial nitric oxide synthase: A ubiquitous regulator of oxidative phosphorylation? Biochem Biophys Res Comm 1996;218:40-44.
6. Xu KY, Huso DL, Dawson T, Bredt DS, Becker LC. NO synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci USA 1999;96:657-662.
7. Rosas GO, Zieman SJ, Donabedian M, Vandegaer K, Hare JM. Augmented age-associated innate immune responses contribute to negative inotropic and lusitropic effects of lipopolysaccharide and interferon gamma. J Mol Cell Cardiol 2001;33:1849-1859.
8. Funakoshi H, Kubota T, Kawamura N, Machida Y, Feldman AM, Tsutsui H, Shimokawa H, Takeshita A. Disruption of inducible nitric oxide synthase improves beta-adrenergic inotropic responsiveness but not the survival of mice with cytokine-induced cardiomyopathy. Circ Res 2002;90:959-965.
9. Hare JM, Givertz MM, Creager MA, Colucci WS. Increased sensitivity to nitric oxide synthase inhibition in patients with heart failure: Potentiation of β-adrenergic inotropic responsiveness. Circulation 1998;97:161-166.
10. Recchia FA, McConnell PI, Bernstein RD, Vogel TR, Xu X, Hintze TH. Reduced nitric oxide production and altered myocardial metabolism during the decompensation of pacing-induced heart failure in the conscious dog. Circ Res 1998;83:969-979.
11. Saavedra WF, Paolocci N, St John ME, Skaf MW, Stewart GC, Xie JS, Harrison RW, Zeichner J, Mudrick D, Marban E, Kass DA, Hare JM. Imbalance between xanthine oxidase and nitric oxide synthase signaling pathways underlies mechanoenergetic uncoupling in the failing heart. Circ Res 2002;90:297-304.
12. Xu L, Eu JP, Meissner G, Stamler JS. Activation of the cardiac calcium release channel (Ryanodine receptor) by Poly-S-Nitrosylation. Science 1998;279:234-237.
13. 2+)-independent nitric oxide synthase in the myocardium. Br J Pharmacol 1992;105:575-580.
14. Balligand J-L, Ungureanu-Longrois D, Simmons WW, Pimental D, Malinski TA, Kapturczak M, Taha Z, Lowenstein CJ, Davidoff AJ, Kelly RA, Smith TW, Michel T. Cytokine-inducible nitric-oxide synthase (iNOS) expression in cardiac myocytes: Characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro. J Biol Chem 1994;269:27580-27588.
15. Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann DL. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: A report from the studies of left ventricular dysfunction (SOLVD). J Am Coll Cardiol 1996;27:1201-1206.
16. Torre-Amione G, Kapadia S, Lee J, Durand J-B, Bies RD, Young JB, Mann DL. Tumor necrosis factor-α and tumor necrosis factor receptors in the failing human heart. Circulation 1996;93:704-711.
17. Heger J, Godecke A, Flogel U, Merx MW, Molojavyi A, Kuhn-Velten WN, Schrader J. Cardiac-specific overexpression of inducible nitric oxide synthase does not result in severe cardiac dysfunction. Circ Res 2002;90:93-99.
18. Ferdinandy P, Danial H, Ambrus I, Rothery RA, Schulz R. Peroxynitrite is a major contributor to cytokine-induced myocardial contractile failure. Circ Res 2000;87:241-247.
19. Shindo T, Ikeda U, Ohkawa F, Kawahara Y, Yokoyama M, Shimada K. Nitric oxide synthesis in cardiac myocytes and fibroblasts by inflammatory cytokines. Cardiovasc Res 1995;29:813-819.
20. Pinsky DJ, Cai B, Yang X, Rodriguez C, Sciacca RR, Cannon PJ. The lethal effects of cytokine-induced nitric oxide on cardiac myocytes are blocked by nitric oxide synthase antagonism or transforming growth factor β. J Clin Invest 1995;95:677-685.
21. Ferdinandy P, Panas D, Schulz R. Peroxynitrite contributes to spontaneous loss of cardiac efficiency in isolated working rat hearts. Am J Physiol 1999;276:H1861-H1867.
22. Oyama J, Shimokawa H, Momii H, Cheng X, Fukuyama N, Arai Y, Egashira K, Nakazawa H, Takeshita A. Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo. J Clin Invest 1998;101;2207-2214.
23. Xie Y-W, Kaminski PM, Wolin MS. Inhibition of rat cardiac muscle contraction and mitochondrial respiration by endogenous peroxynitrite formation during posthypoxic reoxygenation. Circ Res 1998;82:891-897.
24. Szabo C, Ferrer-Sueta G, Zingarelli B, Southan GJ, Salzman AL, Radi R. Mercaptoethylguanidine and guanidine inhibitors of nitric-oxide synthase react with peroxynitrite and protect against peroxynitrite-induced oxidative damage. J Biol Chem 1997;272:9030-9036.
25. Lopez BL, Liu GL, Christopher TA, Ma X. Peroxynitrite, the product of nitric oxide and superoxide, causes myocardial injury in the isolated perfused rat heart. Coronary Artery Disease 1997;8:149-153.
26. Harrison DG. Cellular and molecular mechanisms of endothelial cell dysfunction. J Clin Invest 1997;100:2153-2157.
27. Ito K, Akita H, Kanazawa K, Yamada S, Terashima M, Matsuda Y, Yokoyama M. Comparison of effects of ascorbic acid on endothelium-dependent vasodilation in patients with chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy versus patients with effort angina pectoris secondary to coronary artery disease. Am J Cardiol 1998;82:762-767.
28. Smith CJ, Sun D, Hoegler C, Roth BS, Zhang X, Zhao G, Xu XB, Kobari Y, Pritchard KJ, Sessa WC, Hintze TH. Reduced gene expression of vascular endothelial NO synthase and cyclooxygenase-1 in heart failure. Circ Res 1996;78:58-64.
29. Stein B, Eschenhagen T, Rudiger J, Scholz H, Forstermann U, Gath I. Increased expression of constitutive nitric oxide synthase III, but not inducible nitric oxide synthase II, in human heart failure. J Am Coll Cardiol 1998;32:1179-1186.
30. Fukuchi M, Hussain SN, Giaid A. Heterogeneous expression and activity of endothelial and inducible nitric oxide synthases in end-stage human heart failure: Their relation to lesion site and beta-adrenergic receptor therapy. Circulation 1998;98:132-139.
31. Werner ER, Werner-Felmayer G, Mayer B. Tetrahydrobiopterin, cytokines, and nitric oxide synthesis. Proc Soc Exp Biol Med 1998;219:171-182.
32. Shimizu S, Ishii M, Momose K, Yamamoto T. Role of tetrahydrobiopterin in the function of nitric oxide synthase, and its cytoprotective effect (Review). Int J Mol Med 1998;2:533-540.
33. Cooke JP, Dzau VJ. Derangements of the nitric oxide synthase pathway, L-arginine, and cardiovascular diseases. Circulation 1997;96:379-382.
34. Zieman SJ, Gerstenblith G, Lakatta EG, Rosas GO, Vandegaer K, Ricker KM, Hare JM. Upregulation of the nitric oxide-cGMP pathway in aged myocardium: Physiological response to L-arginine. Circ Res 2001;88:97-102.
35. McNamara DB, Bedi B, Aurora H, Tena L, Ignarro LJ, Kadowitz PJ, Akers DL. L-arginine inhibits balloon catheter-induced intimal hyperplasia. Biochem Biophys Res Commun 1993;193:291-296.
36. Bivalacqua TJ, Hellstrom WJ, Kadowitz PJ, Champion HC. Increased expression of arginase II in human diabetic corpus cavernosum: In diabetic-associated erectile dysfunction. Biochem Biophys Res Commun 2001;283:923-927.
37. Balligand JL, Cannon PJ. Nitric oxide synthases and cardiac muscle. Autocrine and paracrine influences. Arterioscler Thromb Vasc Biol 1997;17:1846-1858.
38. Shah AM, MacCarthy PA. Paracrine and autocrine effects of nitric oxide on myocardial function. Pharmacol Ther 2000;86:49-86.
39. Campbell DL, Stamler JS, 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 1996;108:277-293.
40. Sun J, Xin C, Eu JP, Stamler JS, Meissner G. Cysteine-3635 is responsible for skeletal muscle ryanodine receptor modulation by NO. Proc Natl Acad Sci USA 2001;98:11158-11162.
41. Clementi E, Brown GC, Feelisch M, Moncada S. Persistent inhibition of cell respiration by nitric oxide: Crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proc Natl Acad Sci USA 1998;95:7631-7636.
42. Gross WL, Bak MI, Ingwall JS, Arstall MA, Smith TW, Balligand J-L, Kelly RA. Nitric oxide inhibits creatine kinase and regulates rat heart contractile reserve. Proc Natl Acad Sci USA 1996;93:5604-5609.
43. Moro MA, Darley-Usmar VM, Lizasoain I, Su Y, Knowles RG, Radomski MW, Moncada S. The formation of nitric oxide donors from peroxynitrite. Br J Pharmacol 1995;116:1999-2004.
44. Wu M, Pritchard KA Jr, Kaminski PM, Fayngersh RP, Hintze TH, Wolin MS. Involvement of nitric oxide and nitrosothiols in relaxation of pulmonary arteries to peroxynitrite. Am J Physiol 1994;266:H2108-H2113.
45. Gow AJ, Chen Q, Hess DT, Day BJ, Ischiropoulos H, Stamler JS. Basal and stimulated protein S-nitrosylation in multiple cell types and tissues. J Biol Chem 2002;277:9637-9640.
46. Hess DT, Matsumoto A, Nudelman R, Stamler JS. S-nitrosylation: Spectrum and specificity. Nat Cell Biol 2001;3:E46-E49.
47. Brady AJB, Poole-Wilson PA, Harding SE, Warren JB. Nitric oxide production within cardiac myocytes reduces their contractility in endotoxemia. Am J Physiol 1992;263:H1963-H1966.
48. Paulus WJ, Vantrimpont PJ, Shah AM. Acute effects of nitric oxide on left ventricular relaxation and diastolic distensibility in humans. Assessment by bicoronary sodium nitroprusside infusion. Circulation 1994;89:2070-2078.
49. Mohan P, Brutsaert DL, Paulus WJ. Myocardial contractile response to nitric oxide and cGMP. Circulation 1996;93:1223-1229.
50. Kojda G, Kottenberg K, Noack E. Inhibition of nitric oxide synthase and soluble guanylate cyclase induces cardiodepressive effects in normal rat hearts. Eur J Pharmacol 1997;334:181-190.
51. Kojda G, Kottenberg K. Regulation of basal myocardial function by NO. Cardiovasc Res 1999;41:514-523.
52. Cotton JM, Kearney MT, MacCarthy PA, Grocott-Mason RM, McClean DR, Heymes C, Richardson PJ, Shah AM. Effects of nitric oxide synthase inhibition on basal function and the force-frequency relationship in the normal and failing human heart in vivo. Circulation 2001;104:2318-2323.
53. Hare JM, Lofthouse RA, Juang GJ, Colman L, Ricker KM, Kim B, Senzaki H, Cao S, Tunin RS, Kass DA. Contribution of caveolin protein abundance to augmented nitric oxide signaling in conscious dogs with pacing-induced heart failure. Circ Res 2000;86:1085-1092.
54. Harrison RW, Thakkar RN, Senzaki H, Ekelund UE, Cho E, Kass DA, Hare JM. Relative contribution of preload and afterload to the reduction in cardiac output caused by nitric oxide synthase inhibition with L-N(G)-methylarginine hydrochloride 546C88. Crit Care Med 2000;28:1263-1268.
55. Gyurko R, Kuhlencordt P, Fishman MC, Huang PL. Modulation of mosue cardiac function in vivo by eNOS and ANP. Am J Physiol Heart Circ Physiol 2000;278:H971-H981.
56. Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA, Fishman MC. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 1995;377:239-242.
57. 2+ current in rat ventricular myocytes. J Physiol (Lond) 2001;531:117-130.
58. Gallo MP, Malan D, Bedendi I, Biasin C, Alloatti G, Levi RC. Regulation of cardiac calcium current by NO and cGMP-modulating agents. Pflugers Arch 2001;441:621-628
59. Bartunek J, Shah AM, Vanderheyden M, Paulus WJ. Dobutamine enhances cardiodepressant effects of receptor-mediated coronary endothelial stimulation. Circulation 1997;95:90-96.
60. Heymes C, Vanderheyden M, Bronzwaer JG, Shah AM, Paulus WJ. Endomyocardial nitric oxide synthase and left ventricular preload reserve in dilated cardiomyopathy. Circulation 1999;99:3009-3016.
61. Flesch M, Kilter H, Cremers B, Lenz O, Sudkamp M, Kuhn-Regnier F, Bohm M. Acute effects of nitric oxide and cyclic GMP on human myocardial contractility. J Pharmacol Exp Ther 1997;281:1340-1349.
62. Smith JA, Shah AM, Lewis MJ. Factors released from endocardium of the ferret and pig modulate myocardial contraction. J Physiol 1991;439:1-14.
63. Grocott-Mason R, Anning P, Evans H, Lewis M, Shah A. Modulation of left ventricular relaxation in isolated ejecting heart by endogenous nitric oxide. Am J Physiol 1994;267:H14804-H1813.
64. Anning PB, Grocott-Mason RM, Lewis MJ, Shah AM. Enhancement of left ventricular relaxation in the isolated heart by an angiotensin-converting enzyme inhibitor. Circulation 1995;92:2660-2665.
65. Shah AM, Lewis MJ, Henderson AH. Effects of 8-bromocyclic GMP on contraction and on inotropic response of ferret cardiac muscle. J Mol Cell Cardiol 1991;23:55-64.
66. 2+ in intact cardiac myocytes. Circ Res 1994;74:970-978.
67. Shah AM. Paracrine modulation of heart cell function by endothelial cells. Cardiovasc Res 1996;31:847-867.
68. Vila-Petroff MG, Younes A, Egan J, Lakatta EG, Solott SJ. Activation of distinct cAMP-dependent and cGMP-dependent pathways by nitric oxide in cardiac myocytes. Circ Res 1999;84:1020-1031.
69. Paulus WJ, Vantrimpont PJ, Shah AM. Paracrine coronary endothelial control of left ventricular function in humans. Circulation 1995;92:2119-2126.
70. Dzimiri N. Regulation of beta-adrenoceptor signaling in cardiac function and disease. Pharmacol Rev 1999;51:465-501.
71. 2+ current in single heart cells. Nature 1986;323:273-275.
72. Henning RJ, Khalili IR, Levy MN. Vagal stimulation attenuates sympathetic enhancement of left ventricular function. Am J Physiol 1990;258:H1470-H1475.
73. Hare JM, Kim B, Flavahan NA, Ricker KM, Peng X, Colman L, Weiss RG, Kass DA. Pertussis toxin-sensitive G proteins influence nitric oxide synthase III activity and protein levels in rat heart. J Clin Invest 1998;101:1424-1431.
74. Hare JM, Keaney JF Jr, Balligand JL, Loscalzo J, Smith TW, Colucci WS. Role of nitric oxide in parasympathetic modulation of beta-adrenergic myocardial contractility in normal dogs. J Clin Invest 1995;95(1):360-366.
75. 2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes. Proc Natl Acad Sci USA 1991;88:1197-1201.
76. 2+ current. Involvement of cGMP-inhibited and cGMP-stimulated phosphodiesterases through guanylyl cyclase activity. J Biol Chem 1993;268:26286-26295.
77. 2+ channel during cardiomyogenesis: Switch from NO to adenylyl cyclase-mediated inhibition. FASEB J 1999;13:313-324.
78. Paolocci N, Ekelund UEG, Isoda T, Ozaki M, Vandegaer K, Georgakopoulos D, Harrison R, Kass DA, Hare JM. cGMP-independent inotropic effect of nitric oxide and peroxynitirite donors: Potential role for S-nitrosylation. Am J Physiol 2000;279:H1982-H1988.
79. Balligand J-L, Kelly RA, Marsden PA, Smith TW, Michel T. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc Natl Acad Sci USA 1993;90:347-351
80. Keaney JF Jr, Hare JM, Kelly RA, Loscalzo J, Smith TW, Coluccio W.S. Inhibition of nitric oxide synthase potentiates the positive inotropic response to β-adrenergic stimulation in normal dogs. Am J Physiol 1996;271:H2646-H2652.
81. Kanai AJ, Mesaros S, Finkel MS, Oddis CV, Birder LA, Malinski T. β-Adrenergic regulation of constitutive nitric oxide synthase in cardiac myocytes. Am J Physiol 1997;273:C1371-C1377.
82. 3-adrenoreceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle. J Clin Invest 1998;102:1377-1384.
83. 3-adrenoceptor in the human heart. J Clin Invest 1998;98:556-562.
84. 3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle. J Clin Invest 1998;102:1377-1384.
85. 3-adrenoreceptor agonists. J Pharmacol Exp Ther 1999;290:687-693.
86. Moniotte S, Kobzik L, Feron O, Trochu JN, Gauthier C, Balligand JL. Upregulation of beta(3)-adrenoceptors and altered contractile response to inotropic amines in human failing myocardium. Circulation 2001;103:1649-1655.
87. 3-adrenergic receptor cardiovascular regulation in conscious primates, rats and dogs. J Pharmacol Exp Ther 1996;278:1435-1443.
88. Varghese P, Harrison RW, Lofthouse RA, Georgakopoulos D, Berkowitz DE, Hare JM. Beta(3)-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility. J Clin Invest 2000;106:697-703.
89. Hare JM, Loh E, Creager MA, Colucci WS. Nitric oxide inhibits the contractile response to β-adrenergic stimulation in humans with left ventricular dysfunction. Circulation 1995;92:2198-2203.
90. Wittstein IS, Kass DA, Maughan WL, Pak PH, Fetics B, Hare JM. Cardiac nitric oxide production due to angiotensin converting-enzyme inhibition decreases β-adrenergic myocardial contractility in patients with dilated cardiomyopathy. J Am Coll Cardiol 2001;38:429-435.
91. Prabhu SD, Azimi A, Frosto T. Nitric oxide effects on myocardial function and force-interval relations: Regulation of twitch duration. J Mol Cell Cardiol 1999;31:2077-2085.
92. Prabhu SD, Freeman GL. Effect of tachycardia heart failure on the restitution of left ventricular function in closed-chest dogs. Circulation 1995;91:176-185.
93. Kaye DM, Wiviott SD, Balligand J-L, Simmons WW, Smith TW, Kelly RA. Frequency-dependent activation of a constitutive nitric oxide synthase and regulation of contractile function in adult rat ventricular myocytes. Circ Res 1996;78:217-224.
94. Finkel MS, Oddis CV, Mayer OH, Hattler BG, Simmons R.L. Nitric oxide synthase inhibitor alters papillary muscle force-frequency relationship. J Pharmacol Exp Ther 1995;272:945-952.
95. Harrison RW, Skaf MW, Berkowitz DE, Shoukas AA, Hare JM. Cardiac nitric oxide synthase 1 preserves the force-frequency response in mice. Circulation 2001;104:II436 (Abstract).
96. Ishihara H, Yokota M, Sobue T, Saito H. Relation between ventriculoarterial coupling and myocardial energetics in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 1994;23:406-416.
97. Ekelund UEG, Harrison RW, Shokek O, Thakkar RN, Tunin RS, Senzaki H, Kass DA, Marbán E, Hare JM. Intravenous allopurinol decreases myocardial oxygen consumption and increases mechanical efficiency in dogs with pacing-induced heart failure. Circ Res 1999;85:437-445.
98. Wolff MR, Buck SH, Stoker SW, Greaser ML, Mentzer RM. Myofibrillar calcium sensitivity of isometric tension is increased in human dilated cardiomyopathies: Role of altered beta-adrenergically mediated protein phosphorylation. J Clin Invest 1996;98:167-176.
99. Wolff MR, De Tombe PP, Harasawa Y, Burkhoff D, Bier S, Hunter WC, Gerstenblith G, Kass DA. Alterations in left ventricular mechanics, energetics, and contractile reserve in experimental heart failure. Circ Res 1992;70:516-529.
100. Ide T, Tsutsui H, Kinugawa S, Utsumi H, Kang D, Hattori N, Uchida K, Arimura K, Egashira K, Takeshita A. Mitochondrial electron transport complex I is a potential source of oxygen free radicals in the failing myocardium. Circ Res 1999;85:357-363.
101. Saugstad OD. Role of xanthine oxidase and its inhibitor in hypoxia: Reoxygenation injury. Pediatrics 1996;98:103-107.
102. De Jong JW. Xanthine oxidoreductase activity in perfused hearts of various species, including humans. Circ Res 1990;67:770-773.
103. Cappola TP, Kass DA, Nelson GS, Berger RD, Rosas GO, Kobeissi ZA, Marban E, Hare JM. Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy. Circulation 2001;104:2407-2411.
104. 2+ transport. Circ Res 1995;77:88-97.
105. 2+, and adenine nucleotides under normal and simulated ischemic conditions. Circ Res 1996;79:1100-1109.
106. Clementi E, Brown GC, Foxwell N, Moncada S. On the mechanism by which vascular endothelial cells regulate their oxygen consumption. Proc Natl Acad Sci USA 1999;96:1559-1562.
107. 2 sensor and NO signaling functions. Cell 2000;102:499-509.
108. Eu JP, Xu L, Stamler JS, Meissner G. Regulation of ryanodine receptors by reactive nitrogen species. Biochemical Pharmacology 1999;57:1079-1084.
109. 2+ handling in the dog heart. J Clin Invest 1993;92:823-830.
110. Shinke T, Takaoka H, Takeuchi M, Hata K, Kawai H, Okubo H, Kijima Y, Murata T, Yokoyama M. Nitric oxide spares myocardial oxygen consumption through attenuation of contractile response to beta-adrenergic stimulation in patients with idiopathic dilated cardiomyopathy. Circulation 2000;101:1925-1930.
111. Balligand J-L, Ungureanu D, Kelly RA, Kobzik L, Pimental D, Michel T, Smith TW. Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium. J Clin Invest 1993;91:2314-2319.
112. Lakatta EG. Cardiovascular regulatory mechanisms in advanced age. Physiol Rev 1993;73:413-467.
113. Hare JM, Colucci WS. Role of nitric oxide in the regulation of myocardial function. Prog Cardiovasc Dis 1995;38:155-166.
114. Feron O, Smith TW, Michel T, Kelly RA. Dynamic targeting of the agonist-stimulated m2 muscarinic acetylcholine receptor to caveolae in cardiac myocytes. J Biol Chem 1997;272:17744-17748.
115. Schwencke C, Okumura S, Yamamoto M, Geng YJ, Ishikawa Y. Colocalization of beta-adrenergic receptors and caveolin within the plasma membrane. J Cell Biochem 1999;75:64-72.
116. Schwencke C, Yamamoto M, Okumura S, Toya Y, Kim SJ, Ishikawa Y. Compartmentation of cyclic adenosine 3′,5′-monophosphate signaling in caveolae. Mol Endocrinol 1999;13:1061-1070.
117. Yamamoto M, Okumura S, Oka N, Schwencke C, Ishikawa Y. Downregulation of caveolin expression by cAMP signal. Life Sci 1999;64:1349-1357.
118. Brodde OE. Beta-adrenoceptors in cardiac disease. Pharmacol Ther 1993;60:405-430.
119. Cheng HJ, Zhang ZS, Onishi K, Ukai T, Sane DC, Cheng CP. Upregulation of functional beta(3)-adrenergic receptor in the failing canine myocardium. Circ Res 2001;89:599-606.
120. Hart CY, Hahn EL, Meyer DM, Burnett JC Jr, Redfield MM. Differential effects of natriuretic peptides and NO on LV function in heart failure and normal dogs. Am J Physiol Heart Circ Physiol 2001;281:H146-H154.
121. Senzaki H, Smith CJ, Juang GJ, Isoda T, Mayer SP, Ohler A, Paolocci N, Tomaselli GF, Hare JM, Kass DA. Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure. FASEB J 2001;15:1718-1726.
122. Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DS. Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and α1-syntrophin mediated by PDZ domains. Cell 1996;84:757-767.
123. Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH. Dexras1: A G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Neuron 2000;28:183-193.
124. Kanai AJ, Pearce LL, Clemens PR, Birder LA, VanBibber MM, Choi SY, De Groat WC, Peterson J. Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection. Proc Natl Acad Sci USA 20001;98:14126-14131.
125. Calderone A, Thaik CM, Takahashi N, Chang DLF, Colucci WS. Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts. J Clin Invest 1998;101:812-818.
126. Yang XP, Liu YH, Shesely EG, Bulagannawar M, Liu F, Carretero OA. Endothelial nitric oxide gene knockout mice: Cardiac phenotypes and the effect of angiotensin-converting enzyme inhibitor on myocardial ischemia/reperfusion injury. Hypertension 1999;34:24-30.