title: Mechanisms involved in the vasodilator effect induced by diosgenin in rat superior mesenteric artery.
abstract: The aim of this study was to investigate the vasorelaxant effect induced by diosgenin in superior mesenteric rings. In rings pre-contracted with phenylephrine (10 microM), diosgenin caused concentration-dependent relaxations [EC(50) = (3.3 +/- 1.2) x 10(- 4)M, E(max) = 94.2 +/- 2.6 %]. Vascular relaxation induced by diosgenin was significantly inhibited after removal of the endothelium (E(max) = 46 +/- 8.8%, p < 0.001) or after pre-treatment of the rings with N-nitro-L-arginine methyl esther (l-NAME) 100 or 300 microM (E(max) = 35.3 +/- 4%; 28.1 +/- 3.3%, respectively, p < 0.001), atropine 1 microM (E(max) = 24.6 +/- 3.4%, p < 0.001), hydroxocobalamin 30 microM (E(max) = 54.0 +/- 9.6%, p < 0.001), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) 10 microM (E(max) = 46.0 +/- 8.0%, p < 0.001) or indomethacin 1 microM (E(max) = 22.6 +/- 11.8%, p < 0.001). Vasorelaxation evoked by diosgenin was significantly inhibited after pre-treatment of preparations with both selective and non-selective inhibitors of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels, iberiotoxin 100 nM or tetraethylammonium (TEA) 1mM, respectively (E(max) = 62.5 +/- 9.1%; 65.7 +/- 1.1%, p < 0.001). Conversely, in endothelium-denuded vessels, none of BK(Ca) channel blockers modified the relaxant effect induced by diosgenin. In mesenteric endothelial cells loaded with FURA-2 diosgenin was able to increase intracellular calcium concentrations, which were significantly decreased by atropine 1 microM. In addition, in isolated mesenteric rings, diosgenin induced marked increase in nitric oxide (NO) levels, which was completely abolished after functional endothelium removal. The results obtained here demonstrated that diosgenin-induced relaxation appears to involve endothelial muscarinic receptor activation with increase in intracellular calcium concentrations and consequent release of endothelium-derived relaxing factors (EDRFs), mainly NO and cyclooxygenase derivatives, which activate BK(Ca) channels. Nevertheless, further studies are necessary to clearly elucidate residual endothelium-independent relaxation induced by diosgenin.
authors: Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, Caixa Postal 5009, CEP 58.051-970, João Pessoa-PB, Brazil.
authors: Katy Lísias Gondim
authors: KL
authors: Dias
authors: Nadja de Azevedo
authors: Nde A
authors: Correia
authors: Krísthea Karyne Gonçalves
authors: KK
authors: Pereira
authors: José Maria
authors: JM
authors: Barbosa-Filho
authors: Karla Veruska Marques
authors: KV
authors: Cavalcante
authors: Islania Giselia Albuquerque
authors: IG
authors: Araújo
authors: Darizy Flávia
authors: DF
authors: Silva
authors: Diego Nunes
authors: DN
authors: Guedes
authors: Mario Dos Anjos
authors: Mdos A
authors: Neto
authors: Lusiane Maria
authors: LM
authors: Bendhack
authors: Isac Almeida
authors: IA
authors: Medeiros
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004144:Diosgenin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D045462:Endothelium-Dependent Relaxing Factors / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D045462:Endothelium-Dependent Relaxing Factors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D004144:Diosgenin; D002118:Calcium