ANTAGONISM OF ALPHA(1)-ADRENOCEPTOR AGONIST-INDUCED RESPONSES BY RILMENIDINE IN VASCULAR SMOOTH-MUSCLE

The effect of the centrally acting antihypertensive agent, rilmenidine , was examined on the contractile properties of isolated rat portal ve in strips and on the free cytosolic [Ca2+] ([Ca2+](i)) in isolated myo cytes. Rilmenidine (1-30 mu M) relaxed strips precontracted with norad renaline. This effect was not inhibited by the alpha(2)-adrenoceptor a ntagonist, yohimbine, and was not mimicked by the alpha(2)-adrenocepto r agonist, -N-(45-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,3 04). Rilmenidine dose dependently shifted to the right the concentrati on-response curves to noradrenaline and to phenylephrine but not that to carbachol. Rilmenidine alone (0.1-30 mu M) caused a contraction whi ch maximally corresponded to 18% of the maximal noradrenaline-induced contraction. This effect was not produced by UK 14,304, was not affect ed by yohimbine, but was inhibited by the alpha(1)-adrenoceptor antago nist, prazosin. In isolated myocytes, rilmenidine reduced the noradren aline-induced [Ca2+](i) increase but alone, it produced a rise in [Ca2 +](i), the peak amplitude of which averaged 15% of the noradrenaline-i nduced transient [Ca2+](i) rise. It is concluded that rilmenidine acts as a partial agonist of alpha(1)-adrenoceptors of vascular smooth mus cle, causing relaxation of vessels precontracted by full agonists of a lpha(1)-adrenoceptors. (C) 1998 Elsevier Science B.V.