title: Mechanisms underlying the vasorelaxant effect induced by proanthocyanidin-rich fraction from Croton celtidifolius in rat small resistance arteries.
abstract: Proanthocyanidins are condensed tannins present in fruits, vegetables, and flowers, consumed in the human diet. These compounds are believed to decrease coronary heart disease. The present study was designed to investigate the relaxing effects of a proanthocyanidin-rich fraction (PRF) obtained from Croton celtidifolius BAILL (Euphorbiaceae) barks in rat mesenteric arterial bed (MAB) and isolated mesenteric artery (MA). In the MAB pre-contracted with phenylephrine (Phe), PRF (0.1 - 100 microg) induced a concentration-dependent relaxation of 73% (compared to the control). This effect was significantly reduced by the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG) or high K(+) solution and completely abolished in vessels perfused with KCl plus L-NOARG. However, the vasorelaxant effect was not altered by indomethacin, atropine, yohimbine, pyrilamine, or K(+)-channel blockers: BaCl(2), glibenclamide, ouabain, and 4-aminopyridine. In isolated MA pre-contracted with Phe, PRF also induced a concentration-dependent relaxation (0.1 - 30 microg/mL), which was in turn inhibited by endothelial removal, guanylyl cyclase inhibitor 1H[1,2,3]oxadiazolo[4,3-alpha]quinoxalin, charybdotoxin (ChTx), and ChTx plus apamin. Moreover, the relaxant effect was not altered by HOE140 and apamin given alone. The present study demonstrates that the vasorelaxing effect of PRF is dependent upon the NO-cGMP pathway in combination with hyperpolarization due to activation of Ca(2+)-dependent K(+) channels.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, Brazil.
authors.forename: Silvia
authors.initials: S
authors.lastname: DalBó
authors.forename: Eduardo Gasnhar
authors.initials: EG
authors.lastname: Moreira
authors.forename: Fernanda Costa
authors.initials: FC
authors.lastname: Brandão
authors.forename: Heros
authors.initials: H
authors.lastname: Horst
authors.forename: Moacir Geraldo
authors.initials: MG
authors.lastname: Pizzolatti
authors.forename: Gustavo Amadeu
authors.initials: GA
authors.lastname: Micke
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Ribeiro-do-Valle
mesh_terms: D000818:Animals; D029802:Croton / Q000737:chemistry*; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D024301:Plant Bark / Q000737:chemistry; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D024681:Potassium Channels, Calcium-Activated; D044945:Proanthocyanidins; D014665:Vasodilator Agents; C013221:proanthocyanidin; D009569:Nitric Oxide; D006152:Cyclic GMP