Endothelium-dependent vasoregulation of coronary artery diameter and blood flow.

C oronary vasoregulation, the control of coronary artery diameter and blood flow, is an important and complex physiological function in which the endothelium plays a key role.' Many chemical and mechanical stimuli affect numerous endothelial cell receptors, triggering multiple signal transduction mech- anisms and resulting in the release of several local activators.2 The net effects on coronary artery diameter and blood flow often result from opposing direct smooth muscle and endothelium-mediated actions. Nitric oxide (NO) is thought to be the predominant local endothe- lium-dependent vasodilator.3 In this issue of Circulation, Lefroy et a14 report the effects of intracoronary infusion of N0-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthesis, in 12 normal subjects. In the basal state, L-NMMA reduced distal coronary artery diameter and coronary artery blood flow. As previously demonstrated,5 intracoronary acetylcholine increased distal arterial diameter and blood flow. After L-NMMA infusion, acetylcholine (10-`mol/L) did not increase diameter but did increase coronary blood flow. This study underscores the role of NO in the maintenance of basal arterial diameter and blood flow and, importantly, suggests that acetylcholine regulates resistance vessel diameter through a non-NO mechanism. Interpretation of clinical studies in this complex area requires an understanding of four key issues: differences in the control of arterial diameter and blood flow, stimulus concentration, site specificity, and presence of vascular disease.