Whether phenylephrine exerts inotropic effects through α‐ or β‐adrenoceptors depends upon the relative receptor populations

Abstract

Phenylephrine produced concentration-related positive inotropic responses in isolated left atria and papillary muscles of guinea-pigs and rats. In rat tissues, these responses were unaffected by propranolol but antagonized by prazosin and therefore mediated via .alpha.1-adrenoceptors. The .alpha.1-adrenoceptor agonist methoxamine also exerted positive inotropic effects in these rat tissues. The maximum .alpha.-adrenoceptor-mediated effect of methoxamine (relative to the isoprenaline maximum) was greater than that of phenylephrine in left atria (in the presence of propranolol), whereas in papillary muscles phenylephrine exerted the greater maximum. In guinea-pig papillary muscles, the response to phenylephrine was unaffected by prazosin but was antagonized by propranolol and therefore caused by stimulation of .beta.-adrenoceptors. Methoxamine had no effect in guinea-pig papillary muscles. Guinea-pig left atria produced biphasic concentration-response curves for phenylephrine, the lower portion being antagonized by phentolamine and was therefore .alpha.-adrenoceptor-mediated, while the upper portion was antagonized by propranolol and therefore .beta.-andrenoceptor-mediated. Methoxamine exerted a small inotropic response, the maximum of which was similar to that of the first component of the phenylephrine response. Phenylephrine was a partial agonist for the cardiac .beta.-adrenoceptor. The density of rat ventricular .alpha.-adrencoptors was 4 times greater than .beta.-adrenoceptor density, as measured by [3H]-prazosin and [3H]-dihydroalprenolol binding. This explains why the responses of rat papillary muscles were .alpha.-adrenoceptor-mediated. In contrast, the density of .beta.-adrenoceptor binding sites in guinea-pig ventricles was 6 times greater than the .alpha.-adrenoceptor density. This explains why the phenylephrine responses were .beta.-adrenoceptor-mediated in guinea-pig papillary muscles. In the left atria of guinea-pigs, which displayed both .alpha.- and .beta.-adrenoceptor-mediated responses, the densities of .alpha.- and .beta.-adrenoceptor binding sites were similar. Thus, phenylephrine exerts positive inotropic effects through .alpha.- or .beta.-adrenoceptors depending upon their relative densities.