Pharmacological effects of alpha-methyldopa, alpha-methylnorepinephrine, and octopamine on rat arteriolar, arterial, and terminal vascular smooth.
Experiments on rat mesenteric arterioles, metarterioles, and aortae demonstrate that although alpha-methylnorepinephrine is much less potent in inducing contraction than epinephrine on all three blood vessel types, it is either equivalent or only one and a half to two times less potent than the natural postganglionic neurotransmitter, norepinephrine, on these blood vessels. Furthermore, alpha-methylnorepinephrine is equivalent to norepinephrine in its ability to induce maximal contractile responses on rat arterioles, metarterioles, and aortae. Systemic administration of alpha-methyldopa to rats for 15 days shifted the log dose-response curves for all three catecholamines, but not vasopressin or potassium chloride, to the right of all three blood vessel types; the maximal contractile responses to these amines were, however, not affected by chronic treatment with alpha-methyldopa. In addition, acute, intra-arterial administration of 500 mg/kg of alpha-methyldopa was found not only to induce mesenteric arteriolar vasodilatation gradually but also to depress arteriolar reponsiveness to catecholamines. In view of these direct findings, it is difficult to accept the hypothesis that alpha-methyldopa induces hypotension via formation of a "false" postganglionic neurotransmitter substance, namely, alpha-methylnorepinephrine. The present findings suggest that alpha-methyldopa may exert some of its anti-hypertensive action, at least in the rat, by (1) depressing arteriolar responsiveness to circulating and released catecholamines and (2) some unknown direct action on peripheral vascular muscle. In addition, the present study indicates that octopamine is (1) between 60 and 15,000 times less potent than norepinephrine on rat arterioles and metarterioles and (2) incapable of eliciting more than a 40% occlusion of these terminal vessels. It is suggested that such data support the concept that octopamine, in contrast to alpha-methylnorepinephrine, could serve as a false adrenergic neurotransmitter agent and thus account for part or all of the hypotensive action of monoamine oxidase inhibitors like pargyline. The use of complete dose-response curves, several different adrenergic compounds (i.e., epinephrine, norepinephrine, alpha-methylnorepinephrine, octopamine, phenylephrine, and dopamine), and different rat blood vessels supports the concept that adrenergic molecules containing a catecholamine nucleus and a beta-hydroxyl group elicit the most potent constrictor responses from peripheral blood vessels. In addition, the data suggest that the structure-activity relationships for catecholamines and their analogs on terminal vascular smooth muscle are probably different from those for arterial smooth muscle.[1]References
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