ENDOGENOUS ANGIOTENSIN-II INHIBITS NATRIURESIS AFTER ACUTE VOLUME EXPANSION IN THE NEONATAL RAT

Compared with the adult, the neonatal renal natriuretic response to ac ute volume expansion (VE) is attenuated. To test the hypothesis that a ntinatriuresis is mediated by endogenous angiotensin II (ANG II), Spra gue-Dawley rats were given losartan, an ANG II type 1 (AT(1))- recepto r inhibitor (40 mg . kg(-1). day(-1)) from birth to 14-17 days. Contro l littermates received saline vehicle. Anesthetized rats underwent acu te saline VE for measurement of mean arterial blood pressure (MAP), pl asma aldosterone concentration (P-aldo), plasma atrial natriuretic pep tide (P-ANP), glomerular filtration rate (GFR), sodium excretion (UNaV ), potassium excretion (UKV), and urine guanosine 3',5'-cyclic monopho sphate excretion (UcGMPV) Losartan increased basal urine flow fivefold , UNaV 10-fold, and UKV twofold. Acute VE induced marked diuresis, nat riuresis, and kaliuresis in the losartan but not in the saline group. This occurred without change in P-aldo and P-ANP and despite lower MAP , GFR, and UcGMPV. In addition, losartan did not affect release of cGM P from isolated glomeruli stimulated by ANP or sodium nitroprusside. W e conclude that the limited renal response to acute VE in the neonate results from stimulation of tubular Na reabsorption by ANG II acting o n the AT(1) receptor.