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Warifteine, a bisbenzylisoquinoline alkaloid, induces relaxation by activating potassium channels in vascular myocytes
Author(s) -
Assis Ápio CL,
Araújo Islania GA,
Lima Renata PC,
Almeida Mônica M,
Marinho Alexsandro F,
BarbosaFilho José M,
Cruz Jader S,
Silva Darizy F,
Medeiros Isac A
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12029
Subject(s) - iberiotoxin , glibenclamide , tetraethylammonium , potassium channel , chemistry , alkaloid , vascular smooth muscle , potassium , aorta , 4 aminopyridine , extracellular , potassium channel blocker , endothelium , thoracic aorta , endocrinology , medicine , pharmacology , stereochemistry , biochemistry , smooth muscle , organic chemistry , diabetes mellitus
Summary 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.