Cardiovascular effects of alpha-adrenergic drugs: Differences between clonidine and guanabenz

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Abstract
Guanabenz induced a pressor effect in pithed rats through postsynaptic α2-adrenoceptors whereas clonidine activated both vascular α1 and α2-adrenoceptors. Previous treatment with prazosin, and α1-antagonist, or depletion of the noradrenergic stores by reserpine produced supersensitivity to the pressor response to clondine only, probably through postsynaptic α1-adrenoceptors. The hypotension and bradycardia developed in normotensive rats after intravenous guanabenz administration were abolished by prazosin, whereas the central effects of clonidine were antagonized by both prazosin and yohimbine. Selective destruction of central noradrenergic neurons by [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] (DSP 4) or reserpine plus blockade of catecholamine synthesis by α-methyl-p-tyrosine abolished the hypotension and bradycardia produced by guanabenz but merely reduced the bradycardia from clonidine. The present results suggest that, in rats, guanabenz is a selective stimulant of central α-autoadrenoceptors antagonized by prazosin whereas at a vascular level guanabenz preferentially activates α-adrenoceptors antagonized by yohimbine. The differences observed between the mechanisms by which guanabenz and clonidine produce their central cardiovascular responses might be attributed to their acting on different nuclei.

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