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 histology associated with increased diuresis. In the present study, we assessed the long-term consequences of neonatal angiotensin-converting enzyme 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 concentrating ability, renal function, and renal histology were assessed in 16-week-old rats. There was a twofold increase in diuresis and water intake in enalapril-treated rats throughout the study course. Urine osmolality after 24 hours of water deprivation was 1008 +/- 108 and 2549 +/- 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-1x100 g body wt-1, P < .05) and effective renal plasma flow (1.76 +/- 0.09 versus 2.19 +/- 0.14 mL.min-1x100 g body wt-1, P < .05) were reduced in neonatally enalapril-treated versus control rats. Absolute and fractional urinary sodium excretion values were elevated (P < .05) in enalapril-treated rats. Semiquantitative assessment of renal histology demonstrated statistically significant degrees of papillary atrophy, interstitial fibrosis and inflammation, tubular atrophy and dilatation, and focal glomerulosclerosis in neonatally enalapril-treated rats. In conclusion, neonatal angiotensin-converting enzyme inhibition in the rat produces irreversible alterations in renal function and morphology, demonstrating the importance of an intact renin-angiotensin system neonatally for normal renal development.
Guron
G
G
Department of Physiology, Institute of Physiology and Pharmacology, Göteborg, Sweden.
Adams
M A
MA
Sundelin
B
B
Friberg
P
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004656:Enalapril / Q000009:adverse effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D012964:Sodium / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D012964:Sodium