MODULATION OF CORONARY AUTOREGULATORY RESPONSES BY ENDOTHELIUM-DERIVED NITRIC-OXIDE

There is increasing evidence that endothelium-derived nitric oxide pro duction is an important mechanism contributing to the regulation of my ocardial perfusion during ischemia distal to a coronary stenosis. Stud ies in conscious chronically instrumented animals have extended observ ations in isolated arterioles to demonstrate that inhibiting nitric ox ide synthase with L-arginine analogs increases the vulnerability of th e myocardium to ischemia. The variable extent to which endothelium-dep endent function is impaired in human atherosclerosis raises the possib ility that abnormalities in resistance vessel control contribute to th e functional significance of a fixed epicardial coronary stenosis. Thi s may explain the wide variability between the physiological effects o f a given coronary stenosis and its angiographic severity. Aggressive intervention to normalize endothelium-dependent vasodilation and local nitric oxide release may have beneficial effects on the functional si gnificance of a coronary stenosis.