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 Rg3 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 Rg3 using isolated canine corpus cavernosum. Ginsenoside Rg3 concentration-dependently relaxed the canine corpus cavernosum that had been contracted by phenylephrine (PE), in which IC50 was 1.68 × 10−5 g/ml. Ginsenoside Rg3 significantly (P < 0.05) potentiated acetylcholine (ACh)-induced relaxation in endothelium intact corpus cavernosum. Methylene blue (MB) but not Nω-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 Rg3. Ginsenoside Rg3 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 Rg3 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 Rg3. These results indicate that mechanism responsible for the relaxation by ginsenoside Rg3 is not by stimulating endothelial nitric oxide synthase (eNOS) of the canine corporal smooth muscle but by increasing cyclic nucleotide levels through PDE inhibition.