title: Activation of alpha2-adrenoceptors is necessary to induce nitric oxide release in isoprenaline-induced relaxation.
abstract: The aim of this study was to investigate the role of the contractile agent on the relaxation induced by isoprenaline and the contribution of nitric oxide (NO) and cGMP to this relaxation. These studies were conducted in intact endothelium or denuded aortas contracted with the EC50 of norepinephrine (NE) or phenylephrine (Phe), and the relaxation induced by isoprenaline (non-selective beta-adrenoceptor agonist) or forskolin (activator of adenylyl-cyclase) was studied. The maximum effect (Emax) and pD2 were analysed. Isoprenaline and forskolin-induced relaxation were not changed by the endothelium removal in both NE and Phe-contracted aortas. However, L-NAME reduced the relaxation induced by isoprenaline (Emax from 94.48+/-2.30%, n=7 to 66.17+/-11.73%, n=7; pD2 from 7.56+/-0.10 to 6.08+/-0.15) only in NE-contracted aortas. The pD2 of isoprenaline was also reduced by ODQ (6.57+/-0.13), but not the Emax. The inhibitory effects of L-NAME and ODQ were reversed by yohimbine. L-NAME, ODQ and oxyhemoglobin had no effect on the relaxation induced by isoprenaline in Phe-contracted aortas. Taken together, these results suggest that norepinephrine, a non-selective alpha-adrenoceptor agonist can also activate alpha2-adrenoceptors sensitive to yohimbine in the endothelial cells, activating the NO-synthase and cGMP production which would potentiate the relaxation induced by isoprenaline. However, this pathway is not activated with Phe, the selective alpha1-adrenoceptors agonist.
authors.affiliation: Laboratório de Farmacologia, Dept. Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Ricardo R
authors.initials: RR
authors.lastname: Rascado
authors.forename: Lusiane M
authors.initials: LM
authors.lastname: Bendhack
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000318:Adrenergic beta-Agonists; D018340:Receptors, Adrenergic, alpha-1; D005576:Colforsin; D010656:Phenylephrine; D009569:Nitric Oxide; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine