Proximal tubular function in adult rats treated neonatally with enalapril.

Abstract

Neonatal treatment with angiotensin-converting enzyme (ACE) inhibitors or the angiotensin II type-1 receptor antagonist losartan in rats induces irreversible renal histological abnormalities, mainly papillary atrophy, in association with an impairment in urinary concentrating ability. The aim of the present study was to assess proximal tubular function in adult rats treated neonatally with enalapril. Male Wistar rats received daily, intraperitoneal injections of either enalapril (10 mg kg-1) or isotonic saline vehicle from 3 to 24 days of age. In 15-week-old, hydropenic rats we analysed: (i) proximal tubular iso-osmotic fluid reabsorption using the method of lithium clearance; and (ii) maximal tubular D-glucose reabsorption (TmG), under pentobarbital anaesthesia. The main findings were that neonatally enalapril-treated rats showed: (i) reductions in absolute (APRH2O) and fractional (FPRH2O) iso-osmotic fluid reabsorption in the proximal tubules (APRH2O: 0.50 +/- 0.02 vs. 0.64 +/- 0.03 mL min-1 g KW-1, P < 0.05; FPRH2O: 58 +/- 3 vs. 68 +/- 2%, P < 0.05); and (ii) a normal TmG. In addition, during baseline clearance measurements neonatally enalapril-treated rats showed increases in urine volume and fractional excretion rates of sodium and potassium, a reduction in urine osmolality, whereas glomerular filtration rate and effective renal plasma flow were unaltered. These results suggest that neonatal ACE inhibition produces an irreversible, but differentiated, abnormality in proximal tubular function. Thus, the development of a normal proximal tubular function in the rat seems to be dependent on an intact renin-angiotensin system, (RAS) neonatally.