HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Paulus, W. J. Articles by Bronzwaer, J. G. F. Search for Related Content PubMed PubMed Citation Articles by Paulus, W. J. Articles by Bronzwaer, J. G. F.

INVITED REVIEW: POINT-COUNTERPOINT

Nitric oxide's role in the heart: control of beating or breathing?

Institute for Cardiovascular Research, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands

Submitted 8 December 2003 ; accepted in final form 13 February 2004

ABSTRACT

Beneficial actions of nitric oxide (NO) in failing myocardium have frequently been overshadowed by poorly documented negative inotropic effects mainly derived from in vitro cardiac preparations. NO's beneficial actions include control of myocardial energetics and improvement of left ventricular (LV) diastolic distensibility. In isolated cardiomyocytes, administration of NO increases their diastolic cell length consistent with a rightward shift of the passive length-tension relation. This shift is explained by cGMP-induced phosphorylation of troponin I, which prevents calcium-independent diastolic cross-bridge cycling and concomitant diastolic stiffening of the myocardium. Similar improvements in diastolic stiffness have been observed in isolated guinea pig hearts, in pacing-induced heart failure dogs, and in patients with dilated cardiomyopathy or aortic stenosis and have been shown to result in higher LV preload reserve and stroke work. NO also controls myocardial energetics through its effects on mitochondrial respiration, oxygen consumption, and substrate utilization. The effects of NO on diastolic LV performance appear to be synergistic with its effects on myocardial energetics through prevention of myocardial energy wastage induced by LV contraction against late-systolic reflected arterial pressure waves and through prevention of diastolic LV stiffening, which is essential for the maintenance of adequate subendocardial coronary perfusion. A drop in these concerted actions of NO on diastolic LV distensibility and on myocardial energetics could well be instrumental for the relentless deterioration of failing myocardium.

myocardium; diastole; mitochondria; energetics

This article has been cited by other articles:

				W. H. Wilson Tang, W. Tong, K. Shrestha, Z. Wang, B. S. Levison, B. Delfraino, B. Hu, R. W. Troughton, A. L. Klein, and S. L. Hazen Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure Eur. Heart J., October 2, 2008; 29(20): 2506 - 2513. [Abstract] [Full Text] [PDF]

				R. Fischmeister, L. R.V. Castro, A. Abi-Gerges, F. Rochais, J. Jurevicius, J. Leroy, and G. Vandecasteele Compartmentation of Cyclic Nucleotide Signaling in the Heart: The Role of Cyclic Nucleotide Phosphodiesterases Circ. Res., October 13, 2006; 99(8): 816 - 828. [Abstract] [Full Text] [PDF]

				C. d'Agostino, V. Labinskyy, V. Lionetti, M. P. Chandler, B. Lei, K. Matsuo, M. Bellomo, X. Xu, T. H. Hintze, W. C. Stanley, et al. Altered cardiac metabolic phenotype after prolonged inhibition of NO synthesis in chronically instrumented dogs Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1721 - H1726. [Abstract] [Full Text] [PDF]