EFFECT OF METHYLDOPA, RESERPINE AND GUANETHIDINE ON HINDLEG VASCULAR RESISTANCE

¹ Departments of Internal Medicine and Pharmacology, Division of Clinical Pharmacology, University of Cincinnati College of Medicine, Cincinnati, Ohio, and Department of Pharmacology, Marquette University School of Medicine, Milwaukee, Wisconsin

Flow-pressure curves were obtained in the intact and acutely denervated perfused hindleg of control dogs and those pretreated with one of the three drugs. In control dogs, hindleg pressor responses to bilateral carotid occlusion and to direct sympathetic stimulation were present, and denervation decreased the perfusion pressure at each flow. In dogs pretreated with reserpine or guanethidine, adrenergic nerve blockade was present and denervation did not change the flow-pressure relationships; the curves were indistinguishable from those of the denervated control legs. In contrast, sympathetic responses persisted in dogs pretreated with methyldopa and denervation reduced the perfusion pressures to the same degree as in control dogs; the curves before and after denervation were lower than the corresponding curves in control legs. In addition, intraarterial norepinephrine and -methyl-norepinephrine produced identical pressor responses in denervated hindlegs. These observations suggest a basic difference in the mechanism by which methyldopa and reserpine or guanethidine reduce vascular resistance. Since chronic treatment with methyldopa did not produce adrenergic nerve blockade but lowered hindleg vascular resistance, it appears that this drug reduced vascular resistance through a mechanism which may be unrelated to its effects on the sympathetic nerve endings.