Renal cellular response to ureteral obstruction: role of maturation and angiotensin II

Renal angiotensin II (ANG II) is increased as a result of unilateral ureter al obstruction (WO), and angiotensin AT(2) receptors predominate over AT(1) receptors in the early postnatal period. To examine the renal cellular res ponse to 3-day WO in the neonatal and adult rat, AT(1) and AT(2) receptors were inhibited by losartan and PD-123319, respectively. Additional rats rec eived exogenous ANG II, 0.5 mg.kg(-1).day(-1). Renal cellular proliferation and apoptosis were quantitated by proliferating cell nuclear antigen and t erminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling technique, respectively. In the neonate, UUO reduced proliferation and inc reased tubular apoptosis. Losartan had no detectable cellular effect, where as PD-123319 increased cellular proliferation and suppressed apoptosis, and exogenous ANG II stimulated apoptosis. In the adult, UUO increased cellula r proliferation as well as apoptosis, whereas losartan, PD-123319, and exog enous ANG II did not alter the cellular response. In conclusion, WO impairs renal growth in the neonate by reducing proliferation and stimulating apop tosis, at least in part through angiotensin AT(2) receptors. WO stimulates both renal cellular proliferation and apoptosis in the adult, but these eff ects are independent of ANG II. We speculate that the unique early response s of the developing kidney to urinary tract obstruction are mediated by a h ighly activated renin-angiotensin system and preponderance of AT(2) recepto rs.