Enalapril treatment restores the decreased proximal tubule reabsorption in response to acute volume expansion in diabetic rats.

The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, fluid and electrolyte homeostasis. The RAS is activated and renal interstitial hydrostatic pressure (RIHP) is decreased in diabetic rats. The objective of this study was to evaluate the roles of proximal tubule reabsorption and RAS in the decreased RIHP and blunted natriuretic and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Enalapril was utilized to inhibit angiotensin II (AII) formation. Diabetes mellitus (DM) was induced by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 65 mg/kg). RIHP was measured by a polyethylene (PE) matrix that was chronically implanted in the left kidney. Fractional excretion of phosphate (FE(Pi)) and fractional excretion of lithium (FE(Li)) were used as indexes for proximal tubule reabsorption. VE significantly increased both FE(Li) and FE(Pi) in all groups of rats studied. However, the increase in FE(Li) (DeltaFE(Li)=17.26+/-3.83%) and FE(Pi) (DeltaFE(Pi)=7.38+/-2.37%) in diabetic rats (DC, n=12) were significantly lower as compared with those in nondiabetic control rats (NC, n=8; DeltaFE(Li)=32.15+/-4.71% and DeltaFE(Pi)=20.62+/-3.27%). The blunted increases in FE(Li) and FE(Pi) were associated with an attenuated increase in RIHP (DeltaRIHP) in DC (1.8+/-0.4 mm Hg) compared with NC rats (4.3+/-0.3 mm Hg). Enalapril treatment (25 mg/kg/day in drinking water) had no effect on nondiabetic rats (NE, n=8) as compared with untreated NC rats, but significantly improved RIHP response (DeltaRIHP) to VE in diabetic rats (DE, n=9; 2.8+/-0.5 mm Hg). Both DeltaFE(Li) and DeltaFE(Pi) were restored by enalapril treatment in diabetic rats and no significant differences were found in DeltaFE(Li) and DeltaFE(Pi) between DE (DeltaFE(Li)=26.81+/-4.94% and DeltaFE(Pi)=10.45+/-4.67%) and NC groups of rats in response to VE. These data suggest that the activated RAS and the decrease in RIHP may play an important role in the increased proximal tubule reabsorption, and the attenuated natriuretic and diuretic responses to acute volume expansion in diabetic rats.