Alpha 2-adrenoceptor agonists enhance responses to certain other vasoconstrictor agonists in the rat tail artery.

ABSTRACT

1. The effects of the alpha2-adrenoceptor agonists clonidine, rilmenidine, TL99 and UK14304 on the vasoconstrictor response to sympathetic nerve stimulation and on the concentration-response curves to noradrenaline and phenylephrine were compared in two isolated, perfused vascular tissues the rat tail artery (which has both postjunctional alpha 1- and alpha 2-adrenoceptors), and the rabbit ear artery (in which only alpha 1-adrenoceptors are present postjunctionally). 2. In the rabbit ear artery, the first observable effect of alpha 2-adrenoceptor agonists was inhibition of vasoconstrictor responses to sympathetic nerve stimulation. This occurred with concentrations of the alpha 2-adrenoceptor agonists which were far below those producing vasoconstriction. Responses to noradrenaline were not affected. 3. In contrast, in the rat isolated perfused tail artery, alpha 2-adrenoceptor agonists, in concentrations that produced no other observable effects, enhanced the vasoconstrictor responses to sympathetic nerve stimulation and to noradrenaline. Much higher concentrations of alpha 2-adrenoceptor agonists produced vasoconstriction in most preparations and only then reduced the response to sympathetic nerve stimulation. The enhancing effect of alpha 2-adrenoceptor agonists was blocked by idazoxan, but not by prazosin. 4. Vasoconstrictor responses in the rat tail artery to the relatively selective alpha 1-adrenoceptor agonist phenylephrine were enhanced by alpha 2-adrenoceptor agonists. The enhancement of the response to phenylephrine was greater than that to the mixed alpha 1- and alpha 2-adrenoceptor agonist noradrenaline. 5. Vasoconstrictor responses in the rat tail artery to vasopressin, ATP and KCl, like those to alpha 1-adrenoceptor agonists, were enhanced by alpha 2-adrenoceptor agonists.2+owever, vasoconstrictor responses to