REGULATION OF ANGIOTENSIN-II AT(1) AND AT(2) RECEPTORS IN NEONATAL URETERAL OBSTRUCTION

Chronic unilateral ureteral obstruction (WO) in early development acti vates the intrarenal renin-angiotensin system and leads to profound re nal vasoconstriction, renal growth arrest, and interstitial fibrosis. To investigate the response of the AT(1) and AT(2) subtypes of the ang iotensin II (ANG II) receptors to UUO, Sprague-Dawley rats underwent W O or control sham operation in the first 48 h of life and were studied 1-28 days later. Renal mRNA for renin, AT(1) and AT(2) receptor, and receptor binding and distribution were determined. In contrast to cont rols, renin mRNA increased from 14 to 28 days in the obstructed kidney . After ipsilateral UUO, AT(1) mRNA was suppressed at 1 day, but had i ncreased compared with controls at 28 days. AT(2) receptor mRNA fell r apidly in all kidneys from 1 to 3 days of age, after which it remained undetectable. Compared with the intact opposite kidney, AT(2) mRNA wa s suppressed in the obstructed kidney 1 day after UUO. Compared with c ontrols, AT(1) and AT(2) receptor binding was decreased by ipsilateral UUO at 1 day, whereas AT(1) binding was increased at 28 days. Renal A NG II content was increased in the obstructed compared with the intact opposite kidney 28 days after UUO. In view of the increase in renal r enin and angiotensin II production resulting from UUO, increased renal AT(1) mRNA and receptor binding are likely to contribute to the vasoc onstriction and interstitial fibrosis of the neonatal kidney after pro longed UUO.