Central hypotensive effects of guanfacine in anaesthetized rabbits

Abstract

The effects of intracerebroventricular (i.c.v.) injection of guanfacine, a new antihypertensive agent, on blood pressure and heart rate were investigated and compared with those of clonidine in anaesthetized rabbits. The i.c.v. injection of guanfacine or clonidine induced a decrease in blood pressure and heart rate in doses which were ineffective by an intravenous route. The depressive effect of guanfacine was less than that of clonidine, but the duration of this action was obviously longer than that of clonidine. A fall in heart rate caused by guanfacine was always less conspicuous than that by clonidine in equipotent hypotensive doses. Decrease in blood pressure and heart rate caused by the two drugs were inhibited by i.c.v. pretreatment with phentolamine and 6-hydroxydopamine, respectively. These findings suggest that presynaptic and/or postsynaptic α-adrenoceptors in the brain may play an important role in the hypotension and bradycardia produced by guanfacine as well as clonidine. Furthermore, the uptake mechanism at the presynaptic sites of central noradrenergic neurons may be involved in the mode of hypotensive and bradycardic actions of these two drugs since these effects were abolished by pretreatment with desipramine, an inhibitor of noradrenaline uptake into the presynaptic nerve terminals.