Angiotensin-converting enzyme inhibition in piglets induces persistent renal abnormalities.
1. We have previously shown that neonatal angiotensin-converting enzyme (ACE) inhibition or angiotensin II type 1 (AT1) receptor antagonism during the first three postnatal weeks in the rat produces persistent abnormalities in renal function and histology, indicating an essential role for the renin-angiotensin system (RAS) in normal renal development. 2. The aim of the present study was to investigate whether the pig kidney, which shows a high resemblance to the human kidney, is dependent on an intact RAS neonatally for normal renal development, analogous with findings in rats. 3. Piglets received daily i.p. injections of 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 pigs. 4. Urine osmolality after 20 h water deprivation was 673+/-55 and 928+/-50 mOsm/kg (P<0.05) in enalapril- and vehicle-treated pigs, respectively. There were no significant differences between groups in plasma creatinine or urea concentrations. 5. Semiquantitative analysis of renal histology showed significant 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 normal renal development in the pig, similar to previous observations made in rodents.
Guron
G
G
Department of Physiology, Institute of Physiology and Pharmacology, Göteborg University, Sweden. gregor.guron@fysiologi.gu.se
Sundelin
B
B
Wickman
A
A
Friberg
P
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D007668:Kidney / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D007671:Kidney Concentrating Ability / Q000187:drug effects / Q000502:physiology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D008297:Male; D013552:Swine
D000806:Angiotensin-Converting Enzyme Inhibitors