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 histologic abnormalities and an impaired urinary concentrating ability. The aim 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. Male Wistar rats received daily injections of enalapril (10 mg/kg, intraperitoneally) during different age intervals within 3 to 24 d,of age. Fluid handling and urinary concentrating ability, renal function under pentobarbital anesthesia, and kidney histology using stereologic techniques were evaluated 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 papillary atrophy, and a reduction in the volume of tubular epithelial cells in association with an increase in the proportion of interstitium, throughout the cortex and outer medulla. Functionally, the predominant defect was an impairment in urinary concentrating ability, which correlated with the degree of papillary atrophy. In conclusion, the vulnerable age interval for the induction of irreversible renal abnormalities by enalapril was the first 13 d after birth in the rat. This postnatal time span coincides with the completion of nephrogenesis and a period of marked tubular growth and differentiation, suggesting a pivotal role for angiotensin II in these processes.
Department of Physiology, Institute of Physiology and Pharmacology, Göteborg University, Sweden. gregor.guron@fysiologi.gu.se
G
G
Guron
N
N
Marcussen
A
A
Nilsson
B
B
Sundelin
P
P
Friberg
D000367:Age Factors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D004656:Enalapril / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D007671:Kidney Concentrating Ability / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril