THE MECHANISM OF THE VASODILATOR EFFECT OF RUTAECARPINE, AN ALKALOID ISOLATED FROM EVODIA-RUTAECARPA

The mechanisms underlying the rutaecarpine-induced vasodilatation were studied using isolated rat mesenteric arterial ring segments. The results showed that rutaecarpine (0.1 mu M to 0.1 mM) produced a dose-dependent vasorelaxing response in our preparations, which were precontracted with phenylephrine. This vasodilator effect was significantly attenuated by removal of the endothelium, treatment with L-N-G-nitro-arginine, a nitric oxide synthase inhibitor, and methylene blue, a guanylyl cyclase inhibitor, but not by treatment with atropine, triprolidine and yohimbine. Rutaecarpine pretreatment (1 mu M to 0.1 mM) reduced both the phasic (fast) and tonic (slow) phases of phenylephrine-induced contractions, suggesting that a reduction in intracellular calcium might be involved. It is thus concluded that while the vasorelaxing effect of rutaecarpine appeared to be endothelium-dependent and to involve nitric oxide and guanylyl cyclase, neither muscarinic receptors, histamine H-1 receptors nor alpha(2)-adrenoceptors are involved. Moreover, a direct effect on the vascular smooth muscle cell, possibly through a reduction in intracellular Ca2+, can not be excluded.