Peripheral vascular actions of alpha-methyldopa in the dog

The aim of these study was to investigate peripheral vascular actions of alpha-methyldopa. The following experimental procedures were used: hind-limb of the dog perfused with the animals own blood or with Krebs solution; nictitating membrane of the dog; isolated and perfused segments of the saphenous vein of the dog; superfused strips of the saphenous vein of the dog. In these preparations, effects of alpha-methyldopa on responses elicited by electrical stimulation and on release of 3H-noradrenaline were studied. In dogs pretreated with alpha-methyldopa (200 mg/kg, i.v., 36, 24 and 4 hr before the experiment) contractions of the nictitating membrane caused by cervical sympathetic electrical stimulation were markedly reduced: however, the frequency--response curve to stimulation in the hind-limb and responsiveness to noradrenaline were not significantly different of controls. Perfusion of the hind-limb with Krebs containing alpha-methyldopa (2.2 mM) resulted in a significant reduction of perfusion pressure responses to lumbar sympathetic electrical stimulation with augmented responsiveness to exogenous noradrenaline. Similar results were obtained in in vitro experiments. Effects of alpha-methyldopa were not prevented by cocaine nor by inhibition of decarboxylase by Ro 4-4602 (D,L-serine,2-(2,3,4-,trihydroxybenzyl) hydrazine hydrochloride). Alpha-methyldopa depresses the release of tritiated compounds evoked by electrical stimulation, in saphenous vein strips. This suggests that inhibition of transmitter release could be an important factor to understand peripheral actions of alpha-methyldopa.