NEONATAL ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN THE RAT INDUCES PERSISTENT ABNORMALITIES IN RENAL-FUNCTION AND HISTOLOGY

Recently, we reported that neonatal blockade of the renin-angiotensin system in the rat produces irreversible abnormalities in renal histolo gy associated with increased diuresis. In the present study, we assess ed the long-term consequences of neonatal angiotensin-converting enzym e inhibition on renal function. Rats were injected with 10 mg . kg(-1) . d(-1) enalapril or vehicle from day 3 to day 24 after birth. Urine c oncentrating ability, renal function, and renal histology were assesse d in 16-week-old rats. There was a twofold increase in diuresis and wa ter intake in enalapril-treated rats throughout the study course. Urin e osmolality after 24 hours of water deprivation was 1008+/-108 and 25 49+/-48 mOsm . kg(-1) (P<.05) in enalapril- and vehicle-treated rats, respectively. Glomerular filtration rate (0.54+/-0.03 versus 0.75+/-0. 06 mL . min(-1). 100 g body wt(-1), P<.05) and effective renal plasma flow (1.76+/-0.09 versus 2.19+/-0.14 mL . min(-1). 100 g body wt(-1), P<.05) were reduced in neonatally enalapril-treated versus control rat s. Absolute and fractional urinary sodium excretion values were elevat ed (P<.05) in enalapril-treated rats. Semiquantitative assessment of r enal histology demonstrated statistically significant degrees of papil lary atrophy, interstitial fibrosis and inflammation, tubular atrophy and dilatation, and focal glomerulosclerosis in neonatally enalapril-t reated rats. In conclusion, neonatal angiotensin-converting enzyme inh ibition in the rat produces irreversible alterations in renal function and morphology, demonstrating the importance of an intact renin-angio tensin system neonatally for normal renal development.