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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Effects of 7-day amino acid infusion on renal growth, function, and renin-angiotensin system in fetal sheep

¹Department of Physiology and Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney; and ²Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Australia

Submitted 28 January 2005 ; accepted in final form 10 June 2005

These experiments examined whether renal growth and the fetal renin-angiotensin 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 ± 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 < 0.05), and renal angiotensinogen mRNA levels were 2.6-fold higher (P < 0.005). Circulating renin levels and renal renin mRNA levels were suppressed (P < 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 two-fold higher throughout infusion (P < 0.05). Fractional proximal sodium reabsorption, suppressed at 4 h (from 73.4 ± 6.5 to 53.7 ± 10.2%), did not return to control levels (36.1 ± 3.4% on day 7, P < 0.05). Distal sodium reabsorption was markedly increased (from 79 ± 25 to 261 ± 75 µmol/min by day 7, P < 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, long-term 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

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