Hemodynamic effects of systemic and central administration of alpha-methyldopa

Systemic and regional hemodynamic changes were measured in five restained conscious rhesus monkeys before and after a 2-hour intravenous infusion of 50 mg/kg of alpha-methyldopa and, in another group of five monkeys, 5 to 10 mg injected into a lateral cerebral ventricle. Both routes of administration evoked similar degrees of hypotension, bradycardia and decreased cardiac output, although the cerebral intraventricular (i.c.v.) injections had more immediate and long-lasting effects. Both groups had a similar pattern of changes in the redistribution of cardiac output and blood flow that lasted at least 4 hours. Blood flow was maintained in the hepatic and renal arteries and decreased in skeletal muscle, heart, brain and skin. In contrast, i.c.v. injections of alpha-methyldopamine and alpha-methylnorepinephrine given at the same site evoked dose-related pressor responses that lasted up to 4 hours. The data suggest that alpha-methyldopa has important central action that inhibits sympathetic outflow, but that its hypotensive effect is either mediated only by endogenously formed metabolites or that its mechanism of action is not directly related to these metabolites at sites around the lateral and third cerebral ventricles in the monkey.