Background The role of vascular endothelium in the control of epicardial coronary artery vasomotion during treadmill exercise remains unclear. Therefore, we examined the consequences of in vivo balloon endothelial denudation on external coronary diameter of the left circumflex artery during exercise in conscious dogs.Methods and Results Seven dogs instrumented for the measurement of arterial blood pressure, external coronary artery diameter, and coronary blood flow were studied during exercise before and up to 21 days after balloon endothelial denudation of the proximal left circumflex artery. Endothelial denudation was confirmed by abolition of the epicardial coronary artery dilation induced by acetylcholine (0.3 micrograms/kg IV) and reactive hyperemia. Epicardial coronary vasodilation was observed in the control state during treadmill exercise (+5.2+-1.0%). In contrast, a marked vasoconstriction was observed 3 (-4.6+-0.6%) and up to 6 days after endothelial denudation. Complete epicardial coronary artery dilation in response to acetylcholine and exercise was restored 9 days after endothelial denudation. In addition, epicardial coronary artery vasomotor responses to acetylcholine and treadmill exercise were closely correlated (r=.82, P<.001). Reactive dilation was not completely restored 21 days after endothelial denudation, but reactive hyperemia and exercise vasomotor responses during the 21 days follow-up were correlated (r=.70, P<.001). Vasodilation induced by nitroglycerin (1 micrograms/kg IV) was reduced by 25% (P<.01) 3 days after endothelial denudation and returned to its corresponding control level 3 days later. Prazosin (50 micrograms/kg IV) significantly attenuated the exercise-induced coronary artery constriction after endothelial denudation (+1.5+-1.4% versus -4.6+-1.0%).Conclusions These data demonstrate that endothelium is essential for the mediation of epicardial coronary dilation during exercise and may protect these vessels against the vasoconstrictor effect of endogenous catecholamines. (Circulation. 1994;89:2799-2808.)