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 microM) 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 (> or =10 microM)-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.
Chiou
Wen-Fei
WF
National Research Institute of Chinese Medicine, No. 155-1, Section 2, Li-Nung Street, Shih-Pai, 112, Taipei, Taiwan, ROC. wfchiou@cma23.nricm.edu.tw
Chen
Chieh-Fu
CF
D000375:Aging / Q000502:physiology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009712:Nucleotides, Cyclic / Q000096:biosynthesis; D010413:Penis / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D011817:Rabbits
D020030:Nitric Oxide Donors; D009712:Nucleotides, Cyclic; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D011799:Quinazolines; D009599:Nitroprusside; D005576:Colforsin; C049639:evodiamine; D011188:Potassium