Vasodilator effect of cassiarin a, a novel antiplasmodial alkaloid from Cassia siamea, in rat isolated mesenteric artery

Abstract

The aim of this study was to investigate the vasorelaxant effect induced by cassiarin A, a novel antiplas-modial alkaloid from Cassia siamea, in rings cut from rat superior mesenteric arteries. In rings precontracted with phenylephrine, cassiarin A induced a concentration-dependent relaxation. This relaxation was attenuated: 1) after removal of the endothelium or after pretreatment of rings with 100 μM of NG-nitro-L-arginine (nitric oxide synthase inhibitor) or 10 μM of 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (guanylyl cyclase inhibitor), but not after pretreatment with 10 mM of indomethacin (cyclooxygenase inhibitor); and 2) after pretreatment of preparations with either a nonselective or selective inhibitor of large-conductance Ca2+-activated K+(BKCa) channels [1mM of tetraethylammonium or 100nM of iberiotoxin, respectively]. The cassiarin A-induced relax-ation was also attenuated by these BKCa inhibitors in endothelium-denuded preparations. The cassiarin A-induced relaxation was not altered by treatment with the ATP-sensitive K+-channel inhibitor glibenclamide (10 μM) or with the voltage-dependent K+-channel inhibitor 4-aminopyridine (1mM). In isolated mesenteric artery rings, cassiarin A tended to increase nitric oxide (NO) levels. These results suggest that in the rat mesenteric artery, cassiarin A-induced relaxation may be mediated by endothelial NO and may occur partly via BKCa-channel activation. © 2010 Pharmaceutical Society of Japan.