Antagonism of α1-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 vein strips and on the free cytosolic [Ca2+] ([Ca2+]i) in isolated myocytes. Rilmenidine (1–30 μM) relaxed strips precontracted with noradrenaline. This effect was not inhibited by the α2-adrenoceptor antagonist, yohimbine, and was not mimicked by the α2-adrenoceptor agonist, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304). Rilmenidine dose dependently shifted to the right the concentration–response curves to noradrenaline and to phenylephrine but not that to carbachol. Rilmenidine alone (0.1–30 μM) caused a contraction which maximally corresponded to 18% of the maximal noradrenaline-induced contraction. This effect was not produced by UK 14,304, was not affected by yohimbine, but was inhibited by the α1-adrenoceptor antagonist, prazosin. In isolated myocytes, rilmenidine reduced the noradrenaline-induced [Ca2+]i increase but alone, it produced a rise in [Ca2+]i, the peak amplitude of which averaged 15% of the noradrenaline-induced transient [Ca2+]i rise. It is concluded that rilmenidine acts as a partial agonist of α1-adrenoceptors of vascular smooth muscle, causing relaxation of vessels precontracted by full agonists of α1-adrenoceptors.