Mechanisms of impaired urinary concentrating ability in adult rats treatedneonatally 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 prese nt study was to determine the pathophysiological mechanisms underlying the defect in urine concentration in adult rats treated neonatally with enalapr il. 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-H2O(C)) 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) (148 8 +/- 109 vs. 2858 +/- 110 mosm kg(-l), P < 0.05) and maximal T-H2O(C) were reduced in enalapril- vs. vehicle-treated rats after administration of 1-d esamino-8-D-arginine vasopressin. Neonatally enalapril-treated rats showed marked papillary atrophy, a decrease in medullary tissue solute concentrati ons, and a reduction in AQP2 expression specifically in the inner medulla. Glomerular filtration rate, renal plasma flow and urinary excretion rates o f sodium, potassium and chloride did not differ between groups. In conclusi on, adult rats treated neonatally with enalapril showed a urinary concentra ting defect of renal origin which primarily could be explained by the papil lary atrophy. However, an impaired ability to generate medullary interstiti al hypertonicity, and a decrease in inner medullary AQP2 expression, also s eem to contribute to this defect.