Search

1 The selectivity of a number of agonists for peripheral alpha 1- and alpha 2- adrenoreceptors was determined and related to their cardiovascular effects in pentobarbitone-anaesthetized rats. 2 In isolated tissues, presynaptic alpha 2- and postsynaptic alpha 1-adrenoreceptor activity was determined on the rat vas deferens and anococcygeus muscle respectively. Xylazine, guanabenz, guanoxabenz and guanfacin were more selective, whilst lofexidine, tiamenidine, naphazoline, oxymetazoline and St 91 were less selective than clonidine for presynaptic alpha 2-adrenoreceptors. 3 The anococcygeus muscle of the pithed rat was used to determine the alpha-adrenoreceptor selectivity of the compounds in vivo. The selectivities were similar to those obtained in vitro. 4 Following intravenous administration to pentobarbitone-anaesthetized rats guanabenz and guanfacin caused small transient pressor responses and a prolonged secondary hypotension. In contrast oxymetazoline and St 91 produced marked initial pressor responses and the secondary reduction in blood pressure was absent. Clonidine and tiamenidine produced marked initial pressor responses followed by secondary hypotensive effects. All compounds reduced heart rate. 5 Intracerebroventricular (i.c.v.) administration of clonidine, guanabenz and guanfacin elicited falls in blood pressure and heart rate. In contrast blood pressure was either unaffected or elevated following i.c.v. administration of St 91, oxymetazoline and tiamenidine. 6 It is concluded that in the normotensive rat, central alpha 2-adrenoreceptors play a major role in the hypotensive effects of clonidine and related compounds.