THE CARDIOVASCULAR PHARMACOLOGY OF L(—)-DOPA: PERIPHERAL AND CENTRAL EFFECTS

¹ Department of Pharmacology, Hoffmann-La Roche Inc., Nutley, New Jersey

In the intact dog, the most prominent effects of 10 mg/kg of l-dopa, given i.v., were an increase in myocardial contractile force and heart rate of long duration and a decrease in venous return whereas contractile force was still enhanced. In the venous bypass preparation, l-dopa produced pooling of blood in the venous capacitance bed, whereas the alterations in other cardiovascular parameters were similar to those produced by dopamine. Comparative studies were carried out in dogs with two decarboxylase inhibitors, Ro 4-4602 and MK486, which differ in their peripheral and central activities. The results obtained indicate that the l-dopa-induced positive inotropic and chronotropic effects are mediated chiefly through peripheral mechanisms; the negative inotropic and chronotropic effects appear to be mediated chiefly through central mechanisms. After the administration of MK486 there is a time-related increase in contractile force, heart rate and mean arterial blood pressure during baroreceptor stimulation. All of the cardiovascular effects produced by l-dopa after the administration of MK486 appear to be related to central nervous system hypoxia. A selective blockade of centrally mediated peripheral venomotor outflow by l-dopa is indicated. The peripheral and central cardiovascular actions of l-dopa are due to a catecholamine metabolite, probably dopamine.