Rilmenidine activates postjunctional alpha₁‐ and alpha₂‐adrenoceptors in the canine saphenous vein

Abstract

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 3H-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.

α2‐adrenoceptor ligands inhibit α1‐adrenoceptor‐mediated contraction of isolated rat arteries

“…clonidine > UK 14304 > BHT920; ). This hypothesis is also supported by the observation that rilmenidine may also bind to the α 1A receptor [13]. However, based on the present experiments, rilmenidine appears to show weaker antagonistic properties than the other ligands tested.…”

Cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild‐type and D79N α2A‐adrenoceptor transgenic mice

“…Agonist independent affinity estimates obtained with RS‐79948 suggest that the contractile activity of these agonists, under the conditions employed, was mediated by α 2 ‐adrenoceptors (specifically the α 2A subtype). α 2 ‐Adrenoceptors have been reported previously to mediate, in part, the contractile effect of rilmenidine in this preparation ( Marsault et al ., 1996 ). Lastly, the relative potency of these agonists to contract dog saphenous vein and evoke hypotension in wild‐type mice was essentially the same.…”