Role of endothelin in -adrenoceptor coronary vasoconstriction

Gorman, Mark W., Martin Farias III, Keith N. Richmond, Johnathan D. Tune, and Eric O. Feigl. Role of endothelin in -adrenoceptor coronary vasoconstriction. Am J Physiol Heart Circ Physiol 288: H1937–H1942, 2005. First published December 9, 2004; doi:10.1152/ajpheart.01076.2004.—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 (ET) 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 ETA/ETB 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.