Abstract

The effect of bretylium or cocaine on the positive inotropic action of phenylephrine was investigated on isolated atria from rabbits. In atria in which catecholamines had been almost completely depleted by reserpine, phenylephrine exerted a positive inotropic action which was not significantly different from that observed on normal atria. Bretylium or cocaine blocked the cardiostimulant action of phenylephrine on atria from normal rabbits but had no blocking action on atria depleted of catecholamines by reserpine. After replenishment of the depleted catecholamines by exposing the atria to norepinephrine, the blocking effect of the cardiac action of phenylephrime by bretylium or cocaine was restored. Experiments on atria from rabbits pretreated with graded doses of reserpine show that the less the reduction in myocardial catecholamines, the greater the depression of the action of phenylephrine by bretylium or cocaine. In order to account for these results we propose that bretylium or cocaine may combine with the catecholamine molecule and interfere with the action of phenylephrine at the adrenergic receptor.