Requisite Role of Cardiac Myocytes in Coronary a1-Adrenergic Constriction

Background—a-Adrenergic activation in vivo causes constriction of coronary arterioles, but, paradoxically, in vitro these microvessels do not contract to this stimulus. We hypothesized that cardiac myocytes have a requisite role in a1-adrenergic coronary arteriolar constriction through the release of myocyte-derived contractile factor(s). Methods and Results—Administration of the a1-adrenergic agonist phenylephrine did not constrict isolated coronary arterioles, but constriction was observed to supernatant obtained from phenylephrine-treated cardiac myocytes. Constriction to the supernatant was blocked by administration of an endothelin-A antagonist to the microvessel preparation or an a-adrenergic antagonist to the myocytes and was augmented after administration of an adenosine antagonist. Administration of phenylephrine to the myocytes increased endothelin-1 levels in the supernatant, but only to subthreshold concentrations. Conclusions—Cardiac myocytes have a requisite role in constriction of coronary resistance vessels to a1-adrenergic stimuli, which may be mediated by endothelin-1 and other unidentified myocyte-derived vasoconstrictors. (Circulation. 1998;98:9-12.)