title: Warifteine, a bisbenzylisoquinoline alkaloid, induces relaxation by activating potassium channels in vascular myocytes.
abstract: The present study used functional and electrophysiological approaches to investigate the mechanisms by which warifteine, a bisbenzylisoquinoline alkaloid isolated from Cissampelos sympodialis Eichl., causes vasorelaxation of the rat thoracic aorta. Warifteine (1 pmol/L-10 μmol/L) induced concentration-dependent relaxation (pD(2) = 9.40 ± 0.06; n = 5) of endothelium-intact aortic rings precontracted with noradrenaline (10-100 μmol/L). The relaxation effects were not attenuated by removal of the endothelium. Warifteine also induced the relaxation of prostaglandin F(2α) (1-10 mmol/L)-precontracted rings (pD(2) = 9.2 ± 0.2; n = 8). In contrast, the relaxant activity of warifteine was nearly abolished in high K(+) (80 mmol/L)-precontracted aortic rings. In preparations incubated with 20 mmol/L KCl or with the K(+) channel blockers tetraethylammonium (1, 3 and 5 mmol/L), iberiotoxin (20 nmol/L), 4-aminopyridine (1 mmol/L) or glibenclamide (10 μmol/L), the vasorelaxant activity of warifteine was markedly reduced. However, BaCl(2) (1 mmol/L) had no effect on the relaxant effects of warifteine. In vascular myocytes, warifteine (100 nmol/L) significantly increased whole-cell K(+) currents (at 70 mV). Under nominally Ca(2+) -free conditions, warifteine did not reduce extracellular Ca(2+) -induced contractions in rings precontracted with high K(+) or noradrenaline (100 μmol/L). Together, the results of the present study indicate that warifteine induces potent concentration-dependent relaxation in the rat aorta via an endothelium-independent mechanism that involves the activation of K(+) channels.
authors.affiliation: Laboratory of Pharmaceutical Technology, Federal University of Paraíba, João Pessoa, João Pessoa, Brazil.
authors.forename: Ápio C L
authors.initials: ÁC
authors.lastname: Assis
authors.forename: Islania G A
authors.initials: IG
authors.lastname: Araújo
authors.forename: Renata P C
authors.initials: RP
authors.lastname: Lima
authors.forename: Mônica M
authors.initials: MM
authors.lastname: Almeida
authors.forename: Alexsandro F
authors.initials: AF
authors.lastname: Marinho
authors.forename: José M
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.forename: Jader S
authors.initials: JS
authors.lastname: Cruz
authors.forename: Darizy F
authors.initials: DF
authors.lastname: Silva
authors.forename: Isac A
authors.initials: IA
authors.lastname: Medeiros
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D008297:Male; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D015221:Potassium Channels; D014665:Vasodilator Agents; C003931:warifteine; D015237:Dinoprost; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine