Effects of guanabenz on the adrenergic mechanism in rabbit arterial strips.

Abstract
Guanabenz (2,6-dichlorobenzylidine aminoguanidine acetate) is structurally composed of 2 distinct moeities of clonidine and guanethidine, respectively. This compound lowers the blood pressure and heart rate in experimental animals and humans. Effects of guanabenz on the adrenergic mechanism were studied in isolated rabbit thoracic aorta and pulmonary artery and findings were compared with data obtained with clonidine and guanethidine. Guanabenz in concentrations > 10-6 M produced weak contractions which were attenuated by phentolamine or yohimbine. Such concentrations of guanabenz competitively inhibited the contractile response to noradrenaline [norepinephrine, NE], but did not attenuate the response to tyramine. In concentrations ranging from 10-8 to 10-7 M, guanabenz attenuated the contraction and the increase of 3H-efflux in response to transmural electrical stimulation of the pulmonary artery preincubated with 3H-NE. Phentolamine or yohimbine effectively blocked these inhibitory effects of guanabenz. Such effects of guanabenz were similar to those of clonidine and dissimilar to those of guanethidine. Guanabenz apparently acts on presynaptic and postsynaptic alpha receptors of the peripheral blood vessels, as in the case of clonidine and the potency was almost the same as clonidine.
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