ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN PIGLETS INDUCES PERSISTENT RENAL ABNORMALITIES

1. We have previously shown that neonatal angiotensin-converting enzym e (ACE) inhibition as angiotensin II type 1 (AT(1)) receptor antagonis m during the first three postnatal weeks in the rat produces persisten t abnormalities in renal function and histology, indicating an essenti al role far the renin-angiotensin system (RAS) in normal renal develop ment. 2. The aim of the present study was to investigate whether the p ig kidney, which shows a high resemblance to the human kidney, is depe ndent on an intact RAS neonatally for normal renal development, analog ous with findings in rats, 3. Piglets received daily i.p. injections o f either enalapril (10 mg/kg) or vehicle from 2 to 24 days after birth , Urine concentrating capacity, renal functional parameters and renal histology were assessed in 8-week-old pig, 4. Urine osmolality after 2 0 h water deprivation was 673 +/- 55 and 928 +/- 50 mOsm/kg (P < 0.05) in enalapril- and vehicle-treated pigs, respectively, There were no s ignificant differences between groups in plasma creatinine or urea con centrations, 5. Semiquantitative analysis of renal histology showed si gnificant interstitial fibrosis and inflammation, tubular atrophy and thickened walls of interlobular arteries in enalapril-treated pigs. 6. The present study demonstrates that an intact RAS is required for nor mal renal development in the pig, similar to previous observations mad e in rodents.