Pharmacological profile of evodiamine in isolated rabbit corpus cavernosum

This study was designed to examine the pharmacological properties of evodiamine in isolated rabbit corpus cavernosum. In phenylephrine-precontracted cavernosal strips, evodiamine (0.01-10 muM) induced a concentration-dependent relaxation. Endothelium removal, N-G-nitro-L-arginine methyl ester (L-NAME), or 1-H-[1,2,4]oxadiazolo [4,3-alpha] quinoxalin-1-one (ODQ) treatment did not affect this effect. In endothelium-denuded preparations, evodiamine-evoked response was significantly reduced in 60 mM KCl-precontracted strips and by charybdotoxin treatment, but not by glibenclamide. Higher-concentration evodiamine (greater than or equal to 10 muM)-induced relaxation was also accompanied by an increase in cAMP and cGMP levels, but this effect was not affected by cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine mono-hydrochloride (MDL-12,330A, an adenylyl cyclase inhibitor) or ODQ (a guanylyl cyclase inhibitor), respectively. Evodiamine significantly augmented both the corporal relaxation and the accumulation of cyclic nucleotides to sodium nitroprusside and forskolin, respectively. Evodiamine also enhanced electrical field stimulation-evoked relaxation, and this additive effect was significantly counteracted by zaprinast. In preparations obtained from aged rabbits, evodiamine still elicited complete relaxation; in contrast, acetylcholine- and sodium nitroprusside-evoked maximal response was significantly blunted. In summary, evodiamine possesses a potent corporal relaxing effect which is attributable to endothelium-independent properties probably linked to charybdotoxin-sensitive K+ channel activation in the cavernosal vasculature and by nonselective interfering phosphodiesterase to prevent cyclic nucleotide degradation. Furthermore, the physiological effects of evodiamine on the aged animals may implicate a potential for the treatment of erectile dysfunction. (C) 2002 Elsevier Science B.V. All rights reserved.