EFFECTS OF 3 ALPHA(2)-ADRENOCEPTOR AGONISTS, RILMENIDINE, UK-14304 AND CLONIDINE ON BRADYKININ-INDUCED AND SUBSTANCE-P-INDUCED AIRWAY MICROVASCULAR LEAKAGE IN GUINEA-PIGS

The effects of three alpha(2)-adrenoceptor agonists, clonidine, rilmen idine and UK 14304 on the increase of microvascular permeability induc ed by bradykinin or substance P in guinea-pigs airways have been studi ed in vivo. Extravasation of intravenously (i.v.) injected Evans blue dye was used as index of permeability. The effects of the three alpha( 2)-adrenoceptor agonists on the contraction induced by bradykinin (0.3 mu g. kg(-1), i.v.) and substance P (0.3 mu g. kg(-1), i.v.) were als o studied on the isolated guinea-pig trachea. The increase of plasma e xudation induced by bradykinin (0.3 mu g. kg(-1), i.v.) was inhibited partially by rilmenidine and UK 14304 (20 mu g and 100 mu g, intratrac heally) respectively. These two substances had no action on the effect s of substance P. The effects of rilmenidine and UK 14304 were abolish ed by alpha(2),-blockers (idazoxan 1mg. kg(-1) i.v. and RX 821001 100 mu g. kg(-1), i.v.), but they were not altered by the alpha(1)-blocker prazosin (30 mu g. kg(-1), i.v.). Under similar conditions, clonidine or the alpha(1)-adrenoceptor agonist methoxamine were without signifi cant effects. In vitro, rilmenidine and UK14304 inhibited partially th e contractile effects of bradykinin but not those of substance P. To c onclude, both rilmenidine and UK 14304 inhibit the bradykinin-induced increase of vascular permeability in the airways, and they probably do so on peptidergic nerve endings at the prejunctional level since thes e substances are without effect on substance P. The absence of activit y of clonidine in our study might be due to a difference in spectrum o f action on the several types of alpha(2)-adrenergic or imidazole rece ptors.