SELECTIVE AUGMENTATION OF THE PRESSOR RESPONSES TO CATECHOLAMINES BY METANEPHRINE

¹ Department of Pharmacology, Marquette School of Medicine, Milwaukee, Wisconsin

Metanephrine (5 mg/kg) was found to augment the pressor responses to epinephrine, norepinephrine and -methylnorepinephrine in anesthetized dogs. The augmentation was of short duration, usually lasting less than 45 min. Metanephrine reduced the pressor responses to methoxamine and phenylephrine and had variable effects on the responses to angiotensin and vasopressin. The possibility was considered that the metanephrine-induced augmentation was related to inhibition of catechol-O-methyltransferase (COMT). Metanephrine was found to inhibit dog liver COMT when given in vitro; however, metanephrine failed to alter COMT activity when administered in vivo. The pressor responses induced by the catecholamines were associated with increases in both cardiac output (CO) and total peripheral resistance (TPR). However, metanephrine did not significantly alter the magnitude of the catecholamine-induced increases in CO or TPR. Augmentation of the catecholamine-induced pressor response instead appeared to be principally related to an increase in "base-line TPR" (TPR level immediately before injection of catecholamine) produced by metanephrine. The hemodynamic changes produced by the catecholamines, superimposed on the increase in base-line TPR, resulted in an augmentation of the pressor responses to the catecholamines. Failure of metanephrine to augment the pressor responses to the other agents appears to be due principally to differences in their hemodynamic effects as compared to the catecholamines.