RILMENIDINE ACTIVATES POSTJUNCTIONAL ALPHA(1)-ADRENOCEPTORS AND ALPHA(2)-ADRENOCEPTORS IN THE CANINE SAPHENOUS-VEIN

Experiments were performed to determine the subtypes of alpha-adrenoce ptors involved in the contraction induced by rilmenidine in isolated c anine cutaneous veins. Rings of saphenous vein (without endothelium) w ere suspended for the recording of isometric force in physiological sa lt solution. All experiments were performed in the presence of propran olol (to antagonize beta-adrenoceptors), cocaine (to inhibit neuronal uptake) and hydrocortisone (to inhibit extraneuronal uptake). In the p resence of rauwolscine (an alpha(2)-adrenergic blocker), rilmenidine c aused concentration-dependent contractions which were inhibited by pra zosin (nonselective alpha(1)-antagonist) and by (+)niguldipine (select ive alpha(1A)-adrenergic antagonist), but not by (-)niguldipine. After treatment with phenoxybenzamine (to alkylate alpha(1)-adrenoceptors), rilmenidine evoked contractions of the canine saphenous vein which we re antagonized competitively by rauwolscine. The combination of rauwol scine and prazosin did not abolish contractions evoked by the highest concentrations of rilmenidine. Although binding experiments using H-3- idazoxan suggested the existence of a nonadrenergic binding site (arou nd 20% of the total binding), contractile studies failed to demonstrat e their involvement in the increases in tension evoked by rilmenidine. These experiments suggest that the contractions evoked by rilmenidine in isolated canine veins are mediated by both alpha(1A)- and alpha(2) -adrenoceptors.