EFFECT OF ARGININE DEPLETION ON GLOMERULAR AND TUBULAR KIDNEY-FUNCTION - STUDIES IN ISOLATED PERFUSED RAT KIDNEYS

The effect of L-Arg depletion on glomerular hemodynamics and tubular function of isolated rat kidneys perfused with a medium containing 21 amino acids has been studied. A cyclooxygenase inhibitor was added throughout for blockade of prostaglandin synthesis. Arg depletion caused significant (approximately 30%) reductions in renal perfusion flow rate (PFR, 13.9 +/- 1.2 vs. 19.8 +/- 0.6 ml.min-1.g kidney wt-1), glomerular filtration rate (GFR, 598 +/- 79 vs. 924 +/- 42-mu-l.min-1.g kidney wt-1), and urine flow rate (139 +/- 38 vs. 192 +/- 13-mu-l.min-1.g kidney wt-1) compared with control kidneys, which were perfused with a physiological concentration of Arg (200-mu-M). Filtration fraction (FF) increased with Arg depletion (5.1 +/- 0.4 vs. 4.4 +/- 0.4%). Arg-depleted kidneys had a lower absolute sodium (T(Na), 75.7 +/- 8.8 vs. 107.9 +/- 6.0-mu-mol.min-1.g kidney wt-1) and glucose reabsorption (T(glucose), 3.7 +/- 0.6 vs. 5.6 +/- 0.5-mu-mol.min-1.g kidney wt-1), corresponding to a lower sodium and glucose filtration. Potassium handling and reabsorption of free water were not changed. Oxygen consumption (QO2) was lower in Arg-depleted kidneys (4.6 +/- 0.3 vs. 5.5 +/- 0.5-mu-mol.min-1.g kidney wt-1). The effects of Arg depletion were completely reversed by the addition of Arg (1 mM) at 120 min and partly reversed by the addition of citrulline (1 mM). Ornithine depletion or addition had no effect on PFR, GFR, FF, T(Na), T(glucose), and QO2. N-omega-methyl-L-arginine, a specific inhibitor of nitric oxide endothelium-derived relaxing factor, produced the same effect as Arg depletion. Its effect was fully reversible with L-Arg (1 mM) but not with D-Arg (1 mM). It is concluded that Arg is an important amino acid in the regulation of renal hemodynamics; however, no direct effect on tubular functions could be observed in our model. The metabolic pathway whereby Arg depletion causes the observed changes remains to be clarified.