Peripheral Vascular Actions of α-Methyl-DOPA and Its Mode of Action on Arterioles 1

Abstract

Summary

The present quantitative in vivo and in vitro experiments on rat mesenteric arterioles and aortas, respectively, demonstrate that although α-methylnorepinephrine is much less potent than epinephrine on both types of blood vessels, it is only 1.5-2 times less potent than the natural postganglionic neurotransmitter norepinephrine on these blood vessels. Furthermore, α-methylnorepinephrine is equivalent to norepinephrine in its ability to induce maximal contractile responses on rat arterioles and aortas. Systemic administration of α-methyl-DOPA to rats for 15 days shifted the log dose–response curves for all three catecholamines, but not vasopressin, to the right on both intact 20-30 μm arterioles and isolated aorta; the maximal contractile responses to these amines were, however, not affected by chronic treatment with α-methyl-DOPA. In addition, acute, intra-arterial administration of 500 mg/kg of α-methyl-DOPA was found to not only gradually induce mesenteric arteriolar vasodilatation, but to depress arteriolar responsiveness to catecholamines. In view of these direct findings on intact and isolated blood vessels it is difficult to accept the hypothesis that α-methyl-DOPA induces hypotension via formation of a false transmitter substance—namely, α-methylnorepinephrine. The present findings rather suggest that α-methyl-DOPA may exert some or all of its antihypertensive action by depressing arteriolar responsiveness to circulating and released catecholamines, at least in the rat.

The author is indebted to Dr. B. Berde (Sandoz Ltd.) for the generous supply of synthetic vasopress-in used in this study.