title: The lignan (-)-cubebin inhibits vascular contraction and induces relaxation via nitric oxide activation in isolated rat aorta.
abstract: Cubebin, the most abundant lignan in Piper cubeba, has been described as having several effects as trypanocidal, antimycobacterial, antispasmodic, antimicrobial, anti-inflammatory, and analgesic. This study investigated the vasorelaxant effect produced by (-)-cubebin in isolated rat aortic rings pre-contracted with phenylephrine (Phe), and the possible mechanism involved in this event was evaluated. Endothelium-dependent relaxation was evoked by acetylcholine and (-)-cubebin in intact aortic rings, while endothelium-independent vasorelaxation was elicited by sodium nitroprusside and (-)-cubebin in denuded rings. Cumulative concentration-response curves for Phe (10(-10) -10(-5)  M) were determined for endothelium-intact and endothelium-denuded aortic rings in either the presence or absence of (-)-cubebin. Dose-response curves were also constructed for pre-incubation of vascular rings with Nω-nitro-L-arginine methyl ester (L-NAME) (a non-specific nitric oxide synthase inhibitor), indomethacin (an unspecific cyclooxygenase inhibitor), and 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) (a guanylyl cyclase inhibitor). (-)-Cubebin was found to exert a vasorelaxant effect irrespective of the presence of endothelium, which was abolished by pretreatment with L-NAME and ODQ, but not with indomethacin. In addition, (-)-cubebin was able to reduce Phe contraction in the case of intact rings. These results suggest that (-)-cubebin promotes vasorelaxation via NO/cGMP pathway in rat aorta, without prostacyclin involvement.
authors: Laboratorio de Função Endotelial - Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo, Av do Bandeirantes, 3900, 14.049-900, Ribeirão Preto, SP, Brazil.
authors: Marco Túlio Menezes
authors: MT
authors: Carvalho
authors: Karen Cristina Souza
authors: KC
authors: Rezende
authors: Paulo Roberto Barbosa
authors: PR
authors: Evora
authors: Jairo Kenupp
authors: JK
authors: Bastos
authors: Wilson Roberto
authors: WR
authors: Cunha
authors: Marcio Luis
authors: ML
authors: Andrade E Silva
authors: Andréa Carla
authors: AC
authors: Celotto
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D031701:Piper / Q000737:chemistry; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D017705:Lignans; D011810:Quinoxalines; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP; C433065:cubebin; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin
keywords: aorta; cubebin; lignans; nitric oxide; vasorelaxation