title: Antagonism of alpha1-adrenoceptor agonist-induced responses by rilmenidine in vascular smooth muscle.
abstract: 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 microM) relaxed strips precontracted with noradrenaline. This effect was not inhibited by the alpha2-adrenoceptor antagonist, yohimbine, and was not mimicked by the alpha2-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 microM) 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 alpha1-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 alpha1-adrenoceptors of vascular smooth muscle, causing relaxation of vessels precontracted by full agonists of alpha1-adrenoceptors.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, Valbonne, France.
authors.forename: C
authors.initials: C
authors.lastname: Cario-Toumaniantz
authors.forename: G
authors.initials: G
authors.lastname: Loirand
authors.forename: P
authors.initials: P
authors.lastname: Pacaud
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D000077769:Rilmenidine
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D010080:Oxazoles; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D000077769:Rilmenidine; D002118:Calcium; D009638:Norepinephrine