Endothelial regulation of coronary microvascular tone under physiological and pathophysiological conditions.

The endothelium has profound potential to modulate coronary arteriolar tone under a variety of physiological and pathophysiological situations. The endothelium in coronary microvessels is responsible for producing flow-dependent vasodilation, which is mediated by nitric oxide. The endothelium, however, does not mediate the myogenic response of coronary arterioles, but production of nitric oxide nevertheless modulates myogenic responses. The endothelium also has a role in coronary alpha-adrenergic vasoconstriction, because inhibition of nitric oxide synthesis augments coronary alpha 1 and alpha 2-adrenergic vasoconstriction. Other neurohumoral substances or autocoids also have their vasodilator actions mediated through the production of nitric oxide in coronary arterioles. Specifically, serotonin, adenosine diphosphate, and histamine all have their actions transduced through the production of nitric oxide. In the pathophysiological setting with impaired endothelial function, vasodilator responses to endothelium-dependent factors are significantly attenuated, and this can be reversed by administration of L-arginine. These impaired responses may contribute to the pathogenesis of ischaemic heart disease, especially that which occurs due to microvascular spasm.