Requisite role of cardiac myocytes in coronary alpha1-adrenergic constriction.

BACKGROUND Alpha-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 alpha1-adrenergic coronary arteriolar constriction through the release of myocyte-derived contractile factor(s). METHODS AND RESULTS Administration of the alpha1-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 alpha-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 alpha1-adrenergic stimuli, which may be mediated by endothelin-1 and other unidentified myocyte-derived vasoconstrictors.