© 2000 American Heart Association, Inc.
Review |
Role of Endothelium-Derived Nitric Oxide in the Regulation of Cardiac Oxygen Metabolism
Implications in Health and Disease
From the Department of Physiology (J.-N.T., G.K., T.H.H.), New York Medical College, Valhalla, NY, and Clinique Cardiologique et des Maladies Vasculaires (J.-B.B.), University Hospital of Nantes, France.
Correspondence to Thomas H. Hintze, PhD, New York Medical College, Department of Physiology, Basic Science Building, Valhalla, NY 10595. E-mail thomas_hintze{at}nymc.edu
Abstract—Endothelium-derived NO is considered to be primarily an important determinant of vascular tone and platelet activity; however, the modulation of myocardial metabolism by NO may be one of its most important roles. This modulation may be critical for the regulation of tissue metabolism. Several physiological processes act in concert to make endothelial NO synthase–derived NO potentially important in the regulation of mitochondrial respiration in cardiac tissue, including (1) the nature of the capillary network in the myocardium, (2) the diffusion distance for NO, (3) the low toxicity of NO at physiological (nanomolar) concentrations, (4) the fact that low PO2 in tissue facilitates the action of NO on cytochrome oxidase, and (5) the formation of oxygen free radicals. A decrease in NO production is involved in the pathophysiological modifications that occur in heart failure and diabetes, disease states associated with altered cardiac metabolism that contributes to the evolution of the disease process. In contrast, several drugs (eg, angiotensin-converting enzyme inhibitors, amlodipine, and statins) can restore or maintain endogenous production of NO by endothelial cells, and this mechanism may explain part of their therapeutic efficiency. Thus, the purpose of this review is to critically evaluate the role of NO in the control of mitochondrial respiration, with special emphasis on its effect on cardiac metabolism.
Key Words: endothelial nitric oxide synthase–derived nitric oxide • endothelium • mitochondria • cardiac oxygen consumption
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