It has been proposed that -adrenoceptor vasoconstriction in coronary resistance vessels results not from -adrenoceptors on coronary smooth muscle, but from -adrenoceptors on cardiac myocytes that stimulate endothelin release. The present experiments tested the hypothesis that the -adrenoceptor mediated coronary vasoconstriction that normally occurs during exercise is due to endothelin. In conscious dogs (n=10) the endothelin ET_A/ET_B receptor antagonist tezosentan (1 mg/kg, iv) increased coronary venous oxygen tension at rest but not during treadmill exercise. This result indicates that basal endothelin levels produce a coronary vasoconstriction at rest that is not observed during the coronary vasodilation during exercise. In contrast, the -adrenoceptor antagonist phentolamine increased coronary venous oxygen tension during exercise but not at rest. The difference between the endothelin blockade and -adrenoceptor blockade results indicates that -adrenoceptor coronary vasoconstriction during exercise is not due to endothelin. However, in anesthetized dogs bolus intracoronary injections of the -adrenoceptor agonist phenylephrine produced reductions in coronary blood flow that were partially antagonized by endothelin receptor blockade with tezosentan. These results are best explained if -adrenoceptor-induced endothelin release requires high pharmacological concentrations of catecholamines that are not reached during exercise.