Postnatal time frame for renal vulnerability to enalapril in rats

Angiotensin-converting enzyme inhibition or angiotensin II type 1 receptor blockade in neonatal, but not in weaned, rats induces irreversible renal hi stologic abnormalities and an impaired urinary concentrating ability. The a im of the present study was to define the postnatal time frame when the rat kidney is vulnerable to an interruption of the renin-angiotensin system. M ale Wistar rats received daily injections of enalapril (10 mg/kg, intraperi toneally) during different age intervals within 3 to 24 d,of age. Fluid han dling and urinary concentrating ability, renal function under pentobarbital anesthesia, and kidney histology using stereologic techniques were evaluat ed in adult rats. Enalapril treatment within 3 to 13 d after birth induced abnormalities in renal function and morphology long-term, whereas treatment initiated at 14 d of age did not. The main histologic alterations were pap illary atrophy, and a reduction in the volume of tubular epithelial cells i n association with an increase in the proportion of interstitium, throughou t the cortex and outer medulla. Functionally, the predominant defect was an impairment in urinary concentrating ability, which correlated with the deg ree of papillary atrophy. In conclusion, the vulnerable age interval for th e induction of irreversible renal abnormalities by enalapril was the first 13 d after birth in the rat. This postnatal time span coincides with the co mpletion of nephrogenesis and a period of marked tubular growth and differe ntiation, suggesting a pivotal role for angiotensin II in these processes.