S. Kawashima, K. Hirata, M. Yokoyama
Journal name not available for this finding
Nitric oxide (NO) is one of the most important intracellular messenger molecules with multiple biological functions. The heart contains two cellular components that produce NO, one via constitutive-type nitric oxide synthase (cNOS) and the other via inducible-type NOS (iNOS). Coronary vascular endothelial cells and cardiac myocytes contain both cNOS and iNOS, but coronary vascular smooth muscle cells and leukocytes have only iNOS. In coronary vessels, NO operates as an endothelium-derived relaxing factor (EDRF) and participates in the regulation of the vascular tone of the resistance vessels as well as the epicardial artery. NO is involved not only in the regulation of basal coronary vascular tone but also in the metabolic control of coronary vascular resistance. The impairment of the L-arginine—NO pathway by endothelial dysfunction plays an important role in the pathogenesis of coronary artery disease. The reduced vasodilatory response of the epicardial artery to agonist stimulation may be related to the mechanisms of coronary artery spasm. The impaired metabolic vasodilation is likely to result in abnormal myocardial perfusion. NO is also involved in the regulation of cardiac functions. NO produced via the cNOS-mediated pathway in response to parasympathetic stimulation serves to regulate heart rate and cardiac contractility. The cNOS-derived NO may protect against myocardial injury by preserving coronary flow, inhibiting leukocyte adhesion to endothelium and cardiac myocytes, and inhibiting platelet aggregation. On the other hand, a large amount of NO produced via the iNOS-mediated pathway in cardiac myocytes, leukocytes, and vascular cells is likely to depress cardiac function in pathological conditions in which immune and inflammatory processes are involved.