MYOCARDIAL ALPHA ADRENERGIC RECEPTORS AND THEIR ROLE IN THE PRODUCTION OF A POSITIVE INOTROPIC EFFECT BY SYMPATHOMIMETIC AGENTS

¹ Department of Pharmacology, The University of Texas Southwestern Medical School, Dallas, Texas

The question of the role of myocardial alpha adrenergic receptors in the inotropic effects of sympathomimetic agents has been considered. Phenylephrine was found to produce a two-component positive inotropic effect in guinea-pig atria. The positive inotropic effect of phenylephrine in concentrations up to l0^-6 M was specifically blocked by phentolamine or phenoxybenzamine but not by pronethalol. At higher concentrations of phenylephrine, a second component of activity appeared which was blocked by pronethalol. A portion of the positive inotropic response to epinephrine and norepinephrine was also shown to be blocked by phentolamine or phenoxybenzamine. No such effect could be shown with isoproterenol. The two necessary criteria for an alpha-receptor mediated response have, therefore, been fulfilled. A positive inotropic effect has been shown to be blocked specifically by alpha blocking agents, and the ability of epinephrine anti norepinephrine to produce the effect-has been shown to be greater than that of isoproterenol.