The present study was aimed to investigate whether ginsenoside-Rg3 (Rg3), one of the panaxadiol saponins isolated from Korean ginseng root affects the CA secretion from the perfused model of the isolated rat adrenal gland, and also to clarify its mechanism of action.Design and Method:
The adrenal gland was isolated and perfused with Krebs-bicarbonate. The CA was measured directly by using the fluorospectrophotometer.Results:
Rg3 inhibited ACh-evoked CA secretion in a dose- and time-dependent fashion. Rg3 also time-dependently inhibited the CA secretion evoked by DMPP and high K+. Also, in the presence of Rg3, the CA secretion evoked by veratridine, Bay-K-8644, and cyclopiazonic acid were significantly reduced, respectively. Interestingly, in the simultaneous presence of Rg3 and L-NAME, the inhibitory responses of Rg3 on ACh-evoked CA secretory response was considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of Rg3-treatment alone. The level of NO released from adrenal medulla after the treatment of Rg3 was greatly elevated compared to the basal level. In the simultaneous presence of Rg3 and fimasartan, ACh- and angiotensin II-evoked CA secretory responses were more markedly inhibited in comparison with that of Rg3- or fimasartan-treated alone.Conclusions:
Collectively, these results demonstrate that Rg3 inhibits the CA secretion evoked by stimulation of nicotinic as well as AT1-receptors from adrenal medulla. It seems that this inhibitory effect of Rg3 is mediated by inhibiting both the influx of Ca2+ and Na+ into the adrenochromaffin cells and by reducing Ca2+ release from the cytoplasmic calcium store, at least through the increased NO production due to the activation of NO synthase, which is relevant to neuronal nicotinic receptor blockade. When Rg3 and fimasartan were used in combination, their inhibitory effects were enhanced, which may also be of clinical benefit in treating cardiovascular diseases, including hypertension.