The mechanism of action of stevioside on renal function in rat

Abstract

This research has been performed to elucidate the effect and the mechanism of action of stevioside (SVS ) on the renal function in rats. An intravenous infusion of SVS (150 mg/ml) in the small, medium and large doses (100, 150, 200 mg/kg. BW) reduced blood pressure to the lowest values in the dose-dependent manner within 5-7 min (P<0.001 ). Blood pressure gradually increased afterward! but not to the normal level while heart rate continuously increased in rats treated with the large and medium doses of SVS infusion. The initial decrease of blood pressure could be reversed after preheated with L-NAME whereas both hypotension and tachycardia in the latter period was reversed by pretreatment with indomethacin. Animals pretreated with prazosin reduced blood pressure and heart rate (P<0.001) both before and during SVS infusion while pretreatment with norepinephrine showed the opposite results. The plasma volume and blood volume were not significantly affected during SVS infusion, SVS intubation (2 g/kg. BW) for 6 hours also induced hypotension but with a slight extent. The first 30-min of SVS infusion raised ERBF(P<0.05) without a change of GFR. ERBF was unaltered afterward while GFR reduced (P<0.05) after cessation of SVS infusion in animals treated with the large and medium doses, SVS feeding had no effect on renal hemodynamics. Renal vasodilatation action by SVS infusion could be reversed in rats pretreated with indomethacin or arginine vasopressin (AVP). The congestion of glomerular capillaries from histopathological examination was noted in animals treated with the large and medium doses. The fractional excretion of Na+ (FENa), CI (FECI), glucose (FEG) and K+(FEK) was significantly raised in both during and after SVS infusion. The lithium clearance method showed that the depression of proximal tubular Na+ and water reabsorption correlated to the elevation of FENa The first 30-min of SVS infusion suppressed the renal mitochondrial activity and Na+,K+ATPase activity (P<0.05) approximately 14% and 21% respectively while proximal tubular reabsorption of Na+ reduced 88%. The rise of FENa and FECI remained no matter how a change of renal hemodynamics was occured or not. Pretreatment with indomethacin or AVP reversed the rise of electrolyte excretion during the second period of SVS infusion, SVS intubation also increased electrolyte excretion (P<0.05) without a change of FEG SVS infusion raised the plasma glucose level (PG) (P<0.001) but PG was still lower than the renal plasma threshold of glucose in normal rats (264± 19.25 mg%). Moreover renal tubular reabsorption of glucose during SVS infusion was lower than the tubular transport maximum of glucose (TmG). SVS infusion raised PG by decrease in glucose uptake without a change in insulin release. Hyperglycemic effect of SVS infusion was attenuated after pretreatment with L-NAME or prazosin or indomethacin, but returned to normal after pretreatment with a combination of L-NAME and indomethacin. It can be concluded that the hypotension and tachycardia were mediated via NO, prostaglandin and sympathetic activity during SVS infusion, SVS infusion caused a dilation of both afferent and efferent arterioles. An increase in electrolyte and glucose excretion induced by SVS infusion was the reduction of proximal tubular reabsorption of Na+ whereas svs intubation exerted its effect on distal part of nephron. The hyperglycemic effect by the action of SVS infusion was the interaction among NO, prostaglandin and sympathetic activity, SVS infusion also inhibited glucose-stimulated insulin release.