(Hypertension. 1997;29:91.)
© 1997 American Heart Association, Inc.
Research Articles (Issue 1, Part 1) |
Neonatal Angiotensin-Converting Enzyme Inhibition in the Rat Induces Persistent Abnormalities in Renal Function and Histology
the Department of Physiology, Institute of Physiology and Pharmacology, Göteborg (Sweden) University (G.G., P.F.); Department of Pharmacology and Toxicology, Queens University, Kingston, Canada (M.A.A.); and Department of Pathology, Karolinska Hospital, Stockholm, Sweden (B.S.).
Correspondence to Gregor Guron, Department of Physiology, Institute of Physiology and Pharmacology, Göteborg University, Medicinaregatan 11, S-413 90, Göteborg, Sweden.
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-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 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.
Key Words: angiotensin-converting enzyme • kidney • renin-angiotensin system • rat
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