Warifteine, a bisbenzylisoquinoline alkaloid, induces relaxation by activating potassium channels in vascular myocytes

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.