Effects of 7-day amino acid infusion on renal growth, function, and renin-angiotensin system in fetal sheep.
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 approximately 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 approximately 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 mumol/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.
Boyce
Amanda C
AC
Department of Physiology and Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, Australia. a.boyce@unsw.edu.au
Gibson
Karen J
KJ
Wintour
E Marelyn
EM
Koukoulas
Irene
I
Lumbers
Eugenie R
ER
D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000196:embryology* / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012756:Sheep; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
D000596:Amino Acids