α 2 ‐Adrenoceptor agonists enhance responses to certain other vasoconstrictor agonists in the rat tail artery

1 The effects of the α 2 ‐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 α 1 ‐ and α 2 ‐adrenoceptors), and the rabbit ear artery (in which only α 1 ‐adrenoceptors are present postjunctionally). 2 In the rabbit ear artery, the first observable effect of α 2 ‐adrenoceptor agonists was inhibition of vasoconstrictor responses to sympathetic nerve stimulation. This occurred with concentrations of the α 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, α 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 α 2 ‐adrenoceptor agonists produced vasoconstriction in most preparations and only then reduced the response to sympathetic nerve stimulation. The enhancing effect of α 2 ‐adrenoceptor agonists was blocked by idazoxan, but not by prazosin. 4 Vasoconstrictor responses in the rat tail artery to the relatively selective α 1 ‐adrenoceptor agonist phenylephrine were enhanced by α 2 ‐adrenoceptor agonists. The enhancement of the response to phenylephrine was greater than that to the mixed α 1 ‐ and α 2 ‐adrenoceptor agonist noradrenaline. 5 Vasoconstrictor responses in the rat tail artery to vasopressin, ATP and KCl, like those to α 1 ‐adrenoceptor agonists, were enhanced by α 2 ‐adrenoceptor agonists. However, vasoconstrictor responses to 5‐hydroxytryptamine and angiotensin II were not enhanced.