Contribution of I1‐Imidazoline Receptors and α2‐Adrenoceptors to the Cardiovascular Effects of Intracerebroventricular Moxonidine and Clonidine in Anaesthetized Normotensive Rats

The cardiovascular effects of moxonidine, a novel centrally acting antihypertensive agent which is structurally related to clonidine, were studied in anaesthetized normotensive rats. The relative contribution of I1-imidazoline receptors and α2-adrenoceptors to the effects of moxonidine and clonidine was evaluated in rats pretreated with efaroxan, a mixed I1-imidazoline receptor/α2-adrenoceptor antagonist, or with yohimbine, a selective α2-adrenoceptor antagonist. Intracerebroventricular injections of moxonidine and clonidine decreased blood pressure and heart rate. Pretreatment with efaroxan reduced the hypotensive and bradycardic action of both drugs. Yohimbine attenuated the decrease in blood pressure induced by clonidine, whereas the hypotensive effect of moxonidine was not significantly influenced. The decrease in heart rate after moxonidine or clonidine was not affected by yohimbine. The results suggest that I1-imidazoline receptors are involved in the decrease in blood pressure and heart rate after intracerebroventricular moxonidine and clonidine, while α2-adrenoceptors do not apparently contribute to the heart rate responses to these drugs. Nonetheless, a role of α2-adrenoceptors in the vasodepressor action of intracerebroventricular clonidine is supported by the partial antagonism of clonidine-induced fall in arterial pressure by yohimbine.