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. 2. Warifteine (1 pmol/L–10 lmol/L) induced concentration- dependent relaxation (pD2 = 9.40 ± 0.06; n = 5) of endothelium-intact aortic rings precontracted with noradrenaline (10–100 lmol/L). The relaxation effects were not attenuated by removal of the endothelium. Warifteine also induced the relaxation of prostaglandin F2a (1–10 mmol/L)-precontracted rings (pD2 = 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 lmol/L), the vasorelaxant activity of warifteine was markedly reduced. However, BaCl2 (1 mmol/L) had no effect on the relaxant effects of warifteine. 3. In vascular myocytes, warifteine (100 nmol/L) significantly increased whole-cell K+ currents (at 70 mV). Under nominally Ca2+-free conditions, warifteine did not reduce extracellular Ca2+-induced contractions in rings precontracted with high K+ or noradrenaline (100 lmol/L). 4. 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.