Mechanisms of impaired urinary concentrating ability in adult rats treated neonatally with enalapril.

Neonatal angiotensin-converting enzyme inhibition or angiotensin II type-1 receptor blockade induces irreversible renal histological abnormalities and an impaired urinary concentrating ability in the rat. The aim of the present study was to determine the pathophysiological mechanisms underlying the defect in urine concentration in adult rats treated neonatally with enalapril. Male Wistar rats received daily intraperitoneal injections of enalapril (10 mg kg(-1)) or saline vehicle from 3 to 24 days of age. Assessments of fluid handling and maximal urine osmolality (Uosm(max)), renal function and tubular free water reabsorption (T(c)H2O) under pentobarbital anaesthesia, renal tissue solute concentrations, renal aquaporin-2 (AQP2) expression, and kidney histology, were performed in 12-16-week-old rats. Uosm(max) (1488 +/- 109 vs. 2858 +/- 116 mosm kg(-1), P < 0.05) and maximal T(c)H2O were reduced in enalapril- vs. vehicle-treated rats after administration of 1-desamino-8-D-arginine vasopressin. Neonatally enalapril-treated rats showed marked papillary atrophy, a decrease in medullary tissue solute concentrations, and a reduction in AQP2 expression specifically in the inner medulla. Glomerular filtration rate, renal plasma flow and urinary excretion rates of sodium, potassium and chloride did not differ between groups. In conclusion, adult rats treated neonatally with enalapril showed a urinary concentrating defect of renal origin which primarily could be explained by the papillary atrophy. However, an impaired ability to generate medullary interstitial hypertonicity, and a decrease in inner medullary AQP2 expression, also seem to contribute to this defect.