Cardiovascular effects of alpha-adrenergic drugs: differences between clonidine and guanabenz.
Guanabenz induced a pressor effect in pithed rats through postsynaptic alpha 2-adrenoceptors whereas clonidine activated both vascular alpha 1 and alpha 2-adrenoceptors. Previous treatment with prazosin, an alpha 1-antagonist, or depletion of the noradrenergic stores by reserpine produced supersensitivity to the pressor response to clonidine only, probably through postsynaptic alpha 1-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 alpha-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 alpha-autoadrenoceptors antagonized by prazosin whereas at a vascular level guanabenz preferentially activates alpha-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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003655:Decerebrate State; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006143:Guanabenz / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D006146:Guanidines; D006143:Guanabenz; D003000:Clonidine; D004298:Dopamine; D009638:Norepinephrine