Modulation of coronary autoregulatory responses by endothelium-derived nitric oxide

There is increasing evidence that endothelium-derived nitric oxide production is an important mechanism contributing to the regulation of myocardial perfusion during ischemia distal to a coronary stenosis. Studies in conscious chronically instrumented animals have extended observations in isolated arterioles to demonstrate that inhibiting nitric oxide synthase with l-arginine analogs increases the vulnerability of the myocardium to ischemia. The variable extent to which endothelium-dependent function is impaired in human atherosclerosis raises the possibility that abnormalities in resistance vessel control contribute to the functional significance of a fixed epicardial coronary stenosis. This may explain the wide variability between the physiological effects of 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 significance of a coronary stenosis.