Characterisation of the cardiovascular pharmacology of medetomidine in the horse and sheep

Medetomidine was administered to sheep and horses at a dose rate of 5 mu g kg(-1) (i.v.). Heart rate and blood pressure were recorded. Medetomidine induced bradycardia and a biphasic blood pressure response consisting of a transient hypertension followed by hypotension. Administration of prazosin (an alpha(1) adrenoceptor antagonist; 100 mu g kg(-1), i.v.) had no effect on the cardiovascular response to medetomidine (5 mu g kg(-1), i.v.), but inhibited the cardiovascular response of methoxamine (an alpha(1) adrenoceptor agonist; 75 mu g kg(-1), i.v.). L-659,066 (an alpha(2) adrenoceptor antagonist which does not cross the blood brain barrier; 264 mu g kg(-1), i.v.) attenuated the medetomidine induced bradycardia, but had no effect on the cardiovascular response to methoxamine. L-659,066 also reduced the medetomidine induced hypertension in sheep, but had less effect on the horse. It is concluded that both alpha(1) and alpha(2) adrenoceptors are important in the control of cardiovascular function in horses and sheep. Medetomidine appears to act on alpha(2) adrenoceptors alone in the sheep. The cardiovascular effects of medetomidine in the horse are complex and may be influenced by central alpha(2) adrenoceptor regulation or effects on other receptor subtypes as well as direct stimulation of peripheral alpha(2) adrenoceptors.