. Effects of 7-day amino acid infusion on renal growth, function, and renin-angiotensin system in fetal sheep. Am J Physiol Regul Integr Comp Physiol 289: R1099-R1106, 2005. First published June 16, 2005 doi:10.1152/ajpregu.00055.2005.-These experiments examined whether renal growth and the fetal reninangiotensin system could be stimulated by infusion of amino acids and whether chronic amino acid infusions restored glomerulotubular balance, which had been disrupted during 4-h infusions. Five fetal sheep aged 122 Ϯ 1 days gestation received an infusion of alanine, glycine, proline and serine in 0.15 M saline at 0.22 mmol/min for 7 days. Six control fetuses were given saline at the same rate (5 ml/h). Kidney wet weights after amino acid infusion were 28% larger than control fetuses (P Ͻ 0.05), and renal angiotensinogen mRNA levels were ϳ2.6-fold higher (P Ͻ 0.005). Circulating renin levels and renal renin mRNA levels were suppressed (P Ͻ 0.05), and renal renin protein levels tended to be lower. Arterial pressure was increased, and there was a marked, sustained natriuresis and diuresis. Glomerular filtration rate and filtered sodium were ϳtwo-fold higher throughout infusion (P Ͻ 0.05). Fractional proximal sodium reabsorption, suppressed at 4 h (from 73.4 Ϯ 6.5 to 53.7 Ϯ 10.2%), did not return to control levels (36.1 Ϯ 3.4% on day 7, P Ͻ 0.05). Distal sodium reabsorption was markedly increased (from 79 Ϯ 25 to 261 Ϯ 75 mol/min by day 7, P Ͻ 0.005), but this was not sufficient to restore glomerulotubular balance. The resultant high rates of sodium excretion led to hyponatremia and polyhydramnios. In conclusion, longterm amino acid infusions increased renal angiotensinogen gene expression, kidney weight, and distal nephron sodium reabsorptive capacity but failed to restore proximal and total glomerulotubular balance.fetus; renal function PROTEIN-RICH MEALS AND ACUTE intravenous amino acid infusions have a well-described stimulatory effect on renal function in adult animals and humans, increasing glomerular filtration rate (GFR), renal blood flow (RBF), and tubular reabsorption (16,41,46). Acute amino acid infusions also have marked effects on fetal renal function (26, 45). We have previously reported that during a 4-h infusion of amino acids to lategestation fetal sheep, there were large increases in GFR (50% above control levels) and filtration fraction (FF) and increases in both proximal and distal tubular sodium reabsorption that were sustained for the duration of the infusion (26).In the present study, we continued the 4-h infusion of amino acids for a further 7 days. One of our aims was to find out whether long-term infusion of amino acids would cause the fetal sheep kidney to grow. It is well described that in weanling and adult rats high-protein diets stimulate renal growth, characterized by hypertrophy and hyperplasia of the glomerulus, proximal tubule, and thick ascending limb of the loop of Henle (10, 18, 24, 43). There is evidence that this growth may be partly work induced, related to the increases in glo...