© 1996 American Heart Association, Inc.
Articles |
Nitric Oxide and Cardiac Function
the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Ralph A. Kelly, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. E-mail rakelly@bics.bwh.harvard.edu.
Key Words: endothelial nitric oxide synthase • inducible nitric oxide synthase • signal transduction • autonomic nervous system • heart failure
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Introduction |
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Over the past 5 years there has been an explosion of new information on the physiological and pathophysiological roles of NO within the heart as in other organ systems. In this review, we focus primarily on the regulation of cardiac contractile function by NO. We do not cite many relevant earlier articles (eg, articles on the regulation of cardiac contractility by cyclic nucleotides) that can be accessed directly from references in the manuscripts that are cited, and we ask the forbearance of colleagues whose work has not been cited because of space constraints.
We begin with a brief description of the biochemistry of NO and of each of the three NOS isoforms that have been characterized to date. This is followed by a more detailed overview of the physiological roles of iNOS (or NOS2) and eNOS (or NOS3) in cardiac muscle. We end with a brief review of the effects of pharmacological donors of NO on ICa-L and of possible physiological actions of NO and related congeners that are not thought to be mediated via activation of guanylyl cyclase.
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NOSs |
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The free radical gas, NO, is generated by a family of enzymes known as NOSs that catalyze the conversion of the cationic amino acid L-arginine to L-citrulline in the presence of O2 and NADPH. Depending on the redox status of the cell and the availability of transition metals such as heme iron, low-molecular-weight and -protein thiols, and oxygen-derived free radicals, a number of bioactive derivatives of NO can be
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A. Piech, P. E. Massart, C. Dessy, O. Feron, X. Havaux, N. Morel, J.-L. Vanoverschelde, J. Donckier, and J.-L. Balligand Decreased expression of myocardial eNOS and caveolin in dogs with hypertrophic cardiomyopathy Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H219 - H231. [Abstract] [Full Text] [PDF]
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L. E. Wold, D. P. Relling, J. Duan, F. L. Norby, and J. Ren Abrogated Leptin-Induced Cardiac Contractile Response in Ventricular Myocytes Under Spontaneous Hypertension: Role of JAK/STAT Pathway Hypertension, January 1, 2002; 39(1): 69 - 74. [Abstract] [Full Text] [PDF]
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A. Mebazaa, G. W. De Keulenaer, X. Paqueron, L. J. Andries, P. Ratajczak, S. Lanone, C. Frelin, D. Longrois, D. Payen, D. L. Brutsaert, et al. Activation of Cardiac Endothelium as a Compensatory Component in Endotoxin-Induced Cardiomyopathy: Role of Endothelin, Prostaglandins, and Nitric Oxide Circulation, December 18, 2001; 104(25): 3137 - 3144. [Abstract] [Full Text] [PDF]
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M. T. Ziolo, H. Katoh, and D. M. Bers Expression of Inducible Nitric Oxide Synthase Depresses {beta}-Adrenergic-Stimulated Calcium Release From the Sarcoplasmic Reticulum in Intact Ventricular Myocytes Circulation, December 11, 2001; 104(24): 2961 - 2966. [Abstract] [Full Text] [PDF]
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P. A. MacCarthy, D. J. Grieve, J.-M. Li, C. Dunster, F. J. Kelly, and A. M. Shah Impaired Endothelial Regulation of Ventricular Relaxation in Cardiac Hypertrophy: Role of Reactive Oxygen Species and NADPH Oxidase Circulation, December 11, 2001; 104(24): 2967 - 2974. [Abstract] [Full Text] [PDF]
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L. Dai, P. S. Brookes, V. M. Darley-Usmar, and P. G. Anderson Bioenergetics in cardiac hypertrophy: mitochondrial respiration as a pathological target of NO{middle dot} Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2261 - H2269. [Abstract] [Full Text] [PDF]
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L. A. Nikolaidis, T. Hentosz, A. Doverspike, R. Huerbin, C. Stolarski, Y.-T. Shen, and R. P. Shannon Mechanisms whereby rapid RV pacing causes LV dysfunction: perfusion-contraction matching and NO Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2270 - H2281. [Abstract] [Full Text] [PDF]
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M. T. Ziolo, H. Katoh, and D. M. Bers Positive and negative effects of nitric oxide on Ca2+ sparks: influence of beta -adrenergic stimulation Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2295 - H2303. [Abstract] [Full Text] [PDF]
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A. L. Farre and S. Casado Heart Failure, Redox Alterations, and Endothelial Dysfunction Hypertension, December 1, 2001; 38(6): 1400 - 1405. [Abstract] [Full Text] [PDF]
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W. J. Paulus, S. Frantz, and R. A. Kelly Nitric Oxide and Cardiac Contractility in Human Heart Failure: Time for Reappraisal Circulation, November 6, 2001; 104(19): 2260 - 2262. [Full Text] [PDF]
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J. M. Cotton, M. T. Kearney, P. A. MacCarthy, R. M. Grocott-Mason, D. R. McClean, C. Heymes, P. J. Richardson, and A. M. Shah Effects of Nitric Oxide Synthase Inhibition on Basal Function and the Force-Frequency Relationship in the Normal and Failing Human Heart In Vivo Circulation, November 6, 2001; 104(19): 2318 - 2323. [Abstract] [Full Text] [PDF]
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G. Gulli, R. Cemin, P. Pancera, G. Menegatti, C. Vassanelli, and A. Cevese Evidence of parasympathetic impairment in some patients with cardiac syndrome X Cardiovasc Res, November 1, 2001; 52(2): 208 - 216. [Abstract] [Full Text] [PDF]
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 R D Rakhit and M S Marber Nitric oxide: an emerging role in cardioprotection? Heart, October 1, 2001; 86(4): 368 - 372. [Full Text] [PDF]
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M. Galderisi, G. Vitale, G. Lupoli, M. Barbieri, G. Varricchio, C. Carella, O. de Divitiis, and G. Paolisso Inverse Association Between Free Insulin-Like Growth Factor-1 and Isovolumic Relaxation in Arterial Systemic Hypertension Hypertension, October 1, 2001; 38(4): 840 - 845. [Abstract] [Full Text] [PDF]
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B. D. Hoit Two Faces of Nitric Oxide: Lessons Learned From the NOS2 Knockout Circ. Res., August 17, 2001; 89(4): 289 - 291. [Full Text] [PDF]
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U. K.M. Decking, J. P. Williams, R. Dahmann, T. Stumpe, M. Kelm, and J. Schrader The nitric oxide-induced reduction in cardiac energy supply is not due to inhibition of creatine kinase Cardiovasc Res, August 1, 2001; 51(2): 313 - 321. [Abstract] [Full Text] [PDF]
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Y. Imai, B. Jiang, and A. J Pappano Mechanism for muscarinic inhibition of ICa(L) is determined by the path for elevating cyclic AMP in cardiac myocytes Cardiovasc Res, August 1, 2001; 51(2): 331 - 343. [Abstract] [Full Text] [PDF]
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Y. Kumagai, T. Hayashi, T. Miyauchi, A. Endo, A. Iguchi, M. Kiriya-Sakai, S. Sakai, K. Yuki, M. Kikushima, and N. Shimojo Phenanthraquinone inhibits eNOS activity and suppresses vasorelaxation Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2001; 281(1): R25 - R30. [Abstract] [Full Text] [PDF]
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G. Vandecasteele, I. Verde, C. Rucker-Martin, P. Donzeau-Gouge, and R. Fischmeister Cyclic GMP regulation of the L-type Ca2+ channel current in human atrial myocytes J. Physiol., June 1, 2001; 533(2): 329 - 340. [Abstract] [Full Text] [PDF]
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R. Rastaldo, N. Paolocci, A. Chiribiri, C. Penna, D. Gattullo, and P. Pagliaro Cytochrome P-450 metabolite of arachidonic acid mediates bradykinin-induced negative inotropic effect Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2823 - H2832. [Abstract] [Full Text] [PDF]
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A. Sener and F. G. Smith Nitric oxide modulates arterial baroreflex control of heart rate in conscious lambs in an age-dependent manner Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2255 - H2263. [Abstract] [Full Text] [PDF]
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A. Godecke, T. Heinicke, A. Kamkin, I. Kiseleva, R. H Strasser, U. K M Decking, T. Stumpe, G. Isenberg, and J. Schrader Inotropic response to {beta}-adrenergic receptor stimulation and anti-adrenergic effect of ACh in endothelial NO synthase-deficient mouse hearts J. Physiol., April 1, 2001; 532(1): 195 - 204. [Abstract] [Full Text] [PDF]
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A.C. Mendes Ribeiro, T.M.C. Brunini, J.C. Ellory, and G.E. Mann Abnormalities in L-arginine transport and nitric oxide biosynthesis in chronic renal and heart failure Cardiovasc Res, March 1, 2001; 49(4): 697 - 712. [Abstract] [Full Text] [PDF]
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K. Abe, M. Tokumura, T. Ito, T. Murai, A. Takashima, and N. Ibii Involvement of iNOS in postischemic heart dysfunction of stroke-prone spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H668 - H673. [Abstract] [Full Text] [PDF]
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Y.-P. Wang, H. Xu, K. Mizoguchi, M. Oe, and H. Maeta Intestinal ischemia induces late preconditioning against myocardial infarction: a role for inducible nitric oxide synthase Cardiovasc Res, February 1, 2001; 49(2): 391 - 398. [Abstract] [Full Text] [PDF]
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 D B. Sanders, D. F Larson, K. Hunter, M. Gorman, and B. Yang Comparison of tumor necrosis factor-effect on the expression of iNOS in macrophage and cardiac myocytes Perfusion, January 1, 2001; 16(1): 67 - 74. [Abstract] [PDF]
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 M T Kearney, J M Cotton, P J Richardson, and A M Shah Viral myocarditis and dilated cardiomyopathy: mechanisms, manifestations, and management Postgrad. Med. J., January 1, 2001; 77(903): 4 - 10. [Abstract] [Full Text]
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Y.-T. Xuan, X.-L. Tang, Y. Qiu, S. Banerjee, H. Takano, H. Han, and R. Bolli Biphasic response of cardiac NO synthase isoforms to ischemic preconditioning in conscious rabbits Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2360 - H2371. [Abstract] [Full Text] [PDF]
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