Some paradoxical aspects of the cardiovascular pharmacology of alpha-methyldopa.

In an effort to help explain why it is often difficult to demonstrate hypotension with alpha-methyldopa on an acute basis in normotensive anesthetized animals, the drug was administered intravenously in single doses of either 50, 100, or 200 mg/kg to chloralose-anesthetized cats while monitoring mean arterial pressure; the systolic pressor response in arterial pressure to bilateral occlusion of the common carotid arteries; hind limb vascular resistance in a vascularly isolated, extracorporeally perfused but neurally intact hind limb; and the response of hind limb vascular resistance to CCO. Alpha-methyldopa failed to cause any significant hypotension and also failed to affect vasomotor tone to the hind limb vasculature, but the drug augmented the pressor response to CCO on MAP and hind limb vascular resistance. Alpha-methyldopa also had no effect on hind limb vascular resistance when added directly to the extracorporeally perfused hind limb vascular resistance when added directly to the extracorporeally perfused hind limb circuit, indicating a lack of direct vascular smooth muscle dilating properties in these preparations. It is postulated that the augmented baroreceptor demonstrated may help th explain why it is difficult to record hypotension on an acute experimental basis with this drug. Such actions of alphamethyldopa might also provide a basis for understanding the development of tolerance to the antihypertensive effects of the drug and instances of paradoxical hypertension with it when these occur in the hypertensive human.