Selective blockade by nicergoline of vascular responses elicited by stimulation of alpha(1A)-adrenoceptor subtype in the rat

The alpha(1)-adrenergic blocking activity of nicergoline was re-examined in rats, with a particular emphasis on alpha(1)-adrenoceptor subtypes. In pit hed rats, nicergoline and prazosin infused at a single small dose (0.5 mu g /kg/min i.v.) produced a substantial and identical shift to the right of th e control dose presser response curve to the specific alpha(1)-agonist cira zoline (ED50 = 4.0 +/- 0.1, 4.0 +/- 0.1 and 0.9 +/- 0.01 mu g/kg i.v. for n icergoline, prazosin and vehicle respectively). In the isolated perfused me senteric vascular bed, nicergoline strongly inhibited the presser responses elicited by cirazoline, with approximately 40-fold higher potency (pA(2) = 11.1 +/- 0.3) than prazosin (pA(2) = 9.5 +/- 0.3). Conversely, nicergoline was 20-fold less potent than prazosin to antagonize the contractile effect s of cirazoline in isolated endothelium-denuded aorta (pA(2) = 8.6 +/- 0.2 and 9.9 +/- 0.2 for nicergoline and prazosin respectively). Pretreatment of mesenteric vascular beds with chloroethylclonidine did not significantly m odify nicergoline antagonistic potency (pA(2) = 10.6 +/- 0.2). Nicergoline displaced [H-3]-prazosin bound to rat forebrain membranes pretreated with c hloroethylclonidine (pK(i) = 9.9 +/- 0.2) at concentrations 60-fold lower t han in rat liver membranes (pK(i) = 8.1 +/- 0.2). Finally, of the nicergoli ne metabolites studied, lumilysergol acted as a modest alpha, antagonist (b romonicotinic acid was devoid of alpha(1) antagonist activity). In conclusi on, nicergoline is a potent and selective alpha(1A)-adrenoceptor subtype an tagonist, an alpha(1)-adrenoceptor subtype which is mainly represented in r esistance arteries. (C) Elsevier, Paris.