Endogenous angiotensin II inhibits natriuresis after acute volume expansion in the neonatal rat.
Compared with the adult, the neonatal renal natriuretic response to acute volume expansion (VE) is attenuated. To test the hypothesis that antinatriuresis is mediated by endogenous angiotensin I (ANG II), Sprague-Dawley rats were given losartan, an ANG II type 1 (AT1)-receptor inhibitor (40 mg.kg-1.day-1) from birth to 14-17 days. Control littermates received saline vehicle. Anesthetized rats underwent acute saline VE for measurement of mean arterial blood pressure (MAP), plasma aldosterone concentration (Paldo), plasma atrial natriuretic peptide (PANP), glomerular filtration rate (GFR), sodium excretion (UNaV), potassium excretion (UKV), and urine guanosine 3',5'-cyclic monophosphate excretion (UcGMPV). Losartan increased basal urine flow fivefold, UNaV 10-fold, and UKV twofold. Acute VE induced marked diuresis, natriuresis, and kaliuresis in the losartan but not in the saline group. This occurred without change in Paldo and PANP and despite lower MAP, GFR, and UcGMPV. In addition, losartan did not affect release of cGMP from isolated glomeruli stimulated by ANP or sodium nitroprusside. We conclude that the limited renal response to acute VE in the neonate results from stimulation of tubular Na reabsorption by ANG II acting on the AT1 receptor.
Chevalier
R L
RL
Department of Pediatrics, University of Virginia, Charlottesville 22908, USA.
Thornhill
B A
BA
Belmonte
D C
DC
Baertschi
A J
AJ
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000652:urine*; D000833:Animals, Suckling; D001713:Biphenyl Compounds / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate; D006400:Hematocrit; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D009318:Natriuresis / Q000502:physiology*; D010952:Plasma Substitutes / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D010952:Plasma Substitutes; D013777:Tetrazoles; D000804:Angiotensin II; D012965:Sodium Chloride; D019808:Losartan; D011188:Potassium