OS 31-08 INHIBITORY EFFECTS OF SIMVASTATIN ON CATECHOLAMINE SECRETION FROM THE ADRENAL MEDULLA.

OBJECTIVE: The present study was aimed to investigate the characteristics of simvastatin, one of statins, on the catecholamine (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. CA was measured directly by using the fluorospectrophotometer.

RESULTS: Simvastatin inhibited ACh-evoked CA secretory response in a dose- and time-dependent fashion. Simvastatin also time-dependently inhibited the CA secretion evoked by DMPP and high K. Also, in the presence of simvastatin, the CA secretion evoked by veratridine (a voltage-dependent Na channel activator), Bay-K-8644, and cyclopiazonic acid (a cytoplasmic Ca-ATPase inhibitor) were significantly reduced, respectively. When simvastatin and L-NAME (an inhibitor of NO synthase) were simultaneously treated, the inhibitory responses of simvastatin on ACh-evoked CA secretion were considerably recovered to the extent of the control secretion compared with the case of simvastatin-treatment alone. The level of NO released from adrenal medulla after simvastatin-treatment was greatly elevated compared to the basal released level. Simvastatin-induced inhibitory effect on Ach-evoked CA secretion was not affected by treatment along with mevalonate, the first metabolite of HMG-CoA. However, in the presence of pravastatin, ACh-evoked CA secretion was not influenced.

CONCLUSIONS: Conclusively, above results demonstrate that simvastatin inhibits the CA secretion evoked by stimulation of nicotinic as well as AT1-receptors from adrenal medulla. It seems that this inhibitory effect of simvastatin is mediated by inhibiting both the influx of Ca and Na into the adrenochromaffin cells and also by suppressing Ca release from the cytoplasmic calcium store, at least partly through the increased NO production due to activation of NO synthase, which is relevant to neuronal nicotinic receptor blockade. Simvastatin-induced inhibitory effect of the CA secretion is not thought to be directly associated with the inhibition of HMG-CoA reductase.