REGULATION OF RENAL GROWTH-FACTORS AND CLUSTERIN BY AT(1) RECEPTORS DURING NEONATAL URETERAL OBSTRUCTION

Unilateral ureteral obstruction (UUO) in the neonate impairs growth of the ipsilateral kidney. Since renal renin expression is increased by UUO, we hypothesized that, by activation of AT(1) receptors, angiotens in II (ANG II) regulates expression of transforming growth factor-beta 1 (TGF-beta(1)) and epidermal growth factor (EGF) in the obstructed k idney. Sprague-Dawley rats underwent left UUO or sham operation within the first 48 h of life and received losartan, 40 mg . kg(-1). day(-1) , or saline. After 14 days, steady-state renal mRNA was determined for renin, TGF-beta 1, EGF, and clusterin. Losartan reduced the DNA conte nt of the intact kidneys but did not further decrease that of the obst ructed kidney. Losartan increased renal renin expression and decreased EGF expression by 80%, regardless of UUO. In contrast, losartan reduc ed TGF-beta 1 expression by 34% in obstructed kidneys but did not affe ct TGF-beta 1 in intact kidneys. Losartan increased clusterin expressi on by 60% in obstructed kidneys and sevenfold in intact kidneys. We co nclude that activation of the ANG II AT(1) receptor is necessary for n ormal renal growth and that TGF-beta 1 is regulated by AT(1) receptors in the obstructed, but not intact, kidneys. Through AT(1) receptors, endogenous ANG II stimulates EGF and inhibits clusterin expression.