Responses of coronary vessels to adrenergic stimuli

Coronary responses to adrenergic stimuli were determined in the intact beating heart before and after administration of practolol, 4-(2-hydroxy-3-isopropylaminoproproxy) acetanilide, which in low doses blocks myocardial but not vascular beta receptors. The left circumflex coronary artery of dogs was perfused with arterial blood at constant flow, and coronary perfusion pressure was measured. Before practolol, intracoronary injections of isoproterenol and norepinephrine and electrical stimulation of left cardiac sympathetic nerves caused reductions in perfusion pressure or vasodilatation associated with increases in left ventricular dp/dt, heart rate, and systolic pressure. After practolol, the coronary vasodilator response to isoproterenol was reduced by about 30% and occurred without significant changes in dp/dt, heart rate, and pressures. The addition of propranolol blocked completely the coronary responses to isoproterenol. Vascular responses to isoproterenol in the paw were not altered by practolol. Practolol antagonized the increases in dp/dt, heart rate, and systolic pressure and reversed coronary responses to norepinephrine and nerve stimulation from dilatation to constriction. The constriction, in turn, was reduced or reversed by phentolamine, an alpha receptor antagonist. Propranolol did not augment the constriction seen in response to norepinephrine and nerve stimulation after practolol. These results indicate that the coronary vasodilator action of norepinephrine and sympathetic nerve stimulation is indirect and caused by stimulation of myocardial beta receptors. The direct effect of these two stimuli on coronary vessels is minimal and is mediated through stimulation of alpha (vasoconstrictor) receptors. In contrast, the coronary vasodilator response to isoproterenol is both direct and indirect, resulting from stimulation of vascular and myocardial beta receptors; the direct vascular effect predominated in this study.