CHARACTERIZATION 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. Medet omidine induced bradycardia and a biphasic blood pressure response con sisting of a transient hypertension followed by hypotension. Administr ation 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 me thoxamine (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 medetomidin e induced bradycardia, but had no effect on the cardiovascular respons e to methoxamine. L-659,066 also reduced the medetomidine induced hype rtension in sheep, but had less effect on the horse. It is concluded t hat both alpha(1) and alpha(2) adrenoceptors are important in the cont rol of cardiovascular function in horses and sheep. Medetomidine appea rs to act on alpha(2) adrenoceptors alone in the sheep. The cardiovasc ular effects of medetomidine in the horse are complex and may be influ enced by central alpha(2) adrenoceptor regulation or effects on other receptor subtypes as well as direct stimulation of peripheral alpha(2) adrenoceptors.