Relaxation of canine corporal smooth muscle relaxation by ginsenoside saponin Rg3 is independent from eNOS activation.
It has been reported that nitric oxide (NO) is involved in the relaxation mechanism of ginsenoside saponin in various smooth muscle in experimental animals. Although ginsenoside Rg(3) showed both endothelium-dependent and -independent component relaxation in vascular smooth muscle, the action mechanism of the relaxation of corporal muscle is not clear. We, thus, investigated the relaxation mechanism of ginsenoside Rg(3) using isolated canine corpus cavernosum. Ginsenoside Rg(3) concentration-dependently relaxed the canine corpus cavernosum that had been contracted by phenylephrine (PE), in which IC(50) was 1.68 x 10(-5) g/ml. Ginsenoside Rg(3) significantly (P < 0.05) potentiated acetylcholine (ACh)-induced relaxation in endothelium intact corpus cavernosum. Methylene blue (MB) but not N(omega)-nitro-L-arginine methylester (L-NAME) or ODQ (1H-[1,2,4]oxadiazol-[4,3-]quinoxsalin-1-one) modified the dose-response curve of ginsenoside Rg(3). Ginsenoside Rg(3) also significantly potentiated relaxation response to UV light in the presence of streptozotocin (STZ), which was almost completely (P < 0.01) blocked by ODQ. Ginsenoside Rg(3) concentration-dependently inhibited corporal phosphodiesterases (PDE), which resulted in increase of cyclic adenosine monophosphate (cAMP) as well as cyclic guanosine monophosphate (cGMP) contents in corporal smooth muscles. MB inhibited the accumulation of cGMP but not cAMP by ginsenoside Rg(3). These results indicate that mechanism responsible for the relaxation by ginsenoside Rg(3) is not by stimulating endothelial nitric oxide synthase (eNOS) of the canine corporal smooth muscle but by increasing cyclic nucleotide levels through PDE inhibition.
Kang
Young Jin
YJ
Department of Pharmacology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 660-751, South Korea.
Sohn
Ju-Tae
JT
Chang
Ki Churl
KC
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004285:Dogs; D004727:Endothelium / Q000187:drug effects; D004789:Enzyme Activation; D036145:Ginsenosides / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010413:Penis / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology
D036145:Ginsenosides; D010726:Phosphodiesterase Inhibitors; D012503:Saponins; D010656:Phenylephrine; C097367:ginsenoside Rg3; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP