PROXIMAL TUBULAR FUNCTION IN ADULT RATS TREATED NEONATALLY WITH ENALAPRIL

Neonatal treatment with angiotensin-converting enzyme (ACE) inhibitors or the angiotensin II type-1 receptor antagonist losartan in rats ind uces irreversible renal histological abnormalities, mainly papillary a trophy, in association with an impairment in urinary concentrating abi lity. The aim of the present study was to assess proximal tubular func tion 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-we ek-old, hydropenic rats we analysed. (i) proximal tubular iso-osmotic fluid reabsorption using the method of lithium clearance; and (ii) max imal tubular D-glucose reabsorption (Tm-G), under pentobarbital anaest hesia. The main findings were that neonatally enalapril-treated rats s howed: (i) reductions in absolute (APRH(2)O) and fractional (FPRH2O) i so-osmotic fluid reabsorption in the proximal tubules (APRH(2)O: 0.50 +/- 0.02 vs. 0.64 +/- 0.03 mt min(-1) g KW-1 P < 0.05; FPRH2O: 58 +/- 3 vs. 68 +/- 2%, P < 0.05); and (ii) a normal Tm-G. In addition, durin g baseline clearance measurements neonatally enalapril-treated rats sh owed increases in urine volume and fractional excretion rates of sodiu m and potassium, a reduction in urine osmolality, whereas glomerular f iltration rate and effective renal plasma flow were unaltered. These r esults suggest that neonatal ACE inhibition produces an irreversible, but differentiated, abnormality in proximal tubular function. Thus, th e development of a normal proximal tubular function in the rat seems t o be dependent on an intact renin-angiotensin system, (RAS) neonatally .