Renal cellular response to ureteral obstruction: role of maturation and angiotensin II.
Renal angiotensin II (ANG II) is increased as a result of unilateral ureteral obstruction (UUO), and angiotensin AT(2) receptors predominate over AT(1) receptors in the early postnatal period. To examine the renal cellular response to 3-day UUO in the neonatal and adult rat, AT(1) and AT(2) receptors were inhibited by losartan and PD-123319, respectively. Additional rats received exogenous ANG II, 0.5 mg. kg(-1). day(-1). Renal cellular proliferation and apoptosis were quantitated by proliferating cell nuclear antigen and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling technique, respectively. In the neonate, UUO reduced proliferation and increased tubular apoptosis. Losartan had no detectable cellular effect, whereas PD-123319 increased cellular proliferation and suppressed apoptosis, and exogenous ANG II stimulated apoptosis. In the adult, UUO increased cellular proliferation as well as apoptosis, whereas losartan, PD-123319, and exogenous ANG II did not alter the cellular response. In conclusion, UUO impairs renal growth in the neonate by reducing proliferation and stimulating apoptosis, at least in part through angiotensin AT(2) receptors. UUO stimulates both renal cellular proliferation and apoptosis in the adult, but these effects are independent of ANG II. We speculate that the unique early responses of the developing kidney to urinary tract obstruction are mediated by a highly activated renin-angiotensin system and preponderance of AT(2) receptors.
Department of Pediatrics, University of Virginia, School of Medicine, Charlottesville, Virginia 22908, USA. rlc2m@virginia.edu
R L
RL
Chevalier
B A
BA
Thornhill
J T
JT
Wolstenholme
D000367:Age Factors; D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000166:cytology* / Q000254:growth & development*; D019808:Losartan / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014517:Ureteral Obstruction / Q000503:physiopathology*
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan