Rilmenidine activates postjunctional alpha(1)- and alpha(2)-adrenoceptors in the canine saphenous vein

Experiments were performed to determine the subtypes of alpha-adrenoceptors involved in the contraction induced by rilmenidine in isolated canine cutaneous veins. Rings of saphenous vein (without endothelium) were suspended for the recording of isometric force in physiological salt solution. All experiments were performed in the presence of propranolol (to antagonize beta-adrenoceptors), cocaine (to inhibit neuronal uptake) and hydrocortisone (to inhibit extraneuronal uptake). In the presence of rauwolscine (an alpha(2)-adrenergic blocker), rilmenidine caused concentration-dependent contractions which were inhibited by prazosin (nonselective alpha(1)-antagonist) and by (+)niguldipine (selective 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 were antagonized competitively by rauwolscine. The combination of rauwolscine 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 (around 20% of the total binding), contractile studies failed to demonstrate 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.