Importance of NO/EDRF for glomerular and tubular function: Studies in the isolated perfused rat kidney

Abstract

The effect of the addition of Nω-nitro-L-arginine (L-NNA, 10 and 100 μM) to isolated rat kidneys perfused with a complex medium containing 21 amino acids has been studied. A cyclooxygenase inhibitor was added throughout to block prostaglandin synthesis. L-NNA caused significant reductions in renal perfusion flow rate (PFR, 9.8 ± 1.4 vs. 15.9 ± 1.1 ml · min-1 · g kidney wt-1, P < 0.0001), glomerular filtration rate (GFR, 566 ± 57 vs. 705 ± 47 μl · min-1 · g kidney wt-1, P < 0.05) and an increase in the relative filtration fraction (%FF, 7.0 ± 0.6 vs. 5.2 ± 0.4%, P < 0.05) compared to control kidneys. L-NNA pertused kidneys had a lower absolute sodium (72 ± 9 vs. 88 ± 4 μmol · min-1 · g kidney wt-1, P < 0.05) and glucose reabsorption (3.5 ± 0.5 vs. 5.4 ± 0.4 μmol · min-1 · g kidney wt-1, P < 0.05), corresponding mainly to a lower sodium and glucose filtration. However, the relative reabsorption of sodium and glucose in the presence of L-NNA was attenuated, too (82.8 ± 2.0 vs. 87.0 ± 3.3% P < 0.05 and 91.3 ± 1.1 vs. 94.1 ± 0.5%, P < 0.05). Potassium handling and protein excretion were not changed significantly; fractional protein excretion increased slightly with the addition of L-arginine (47 ± 5 vs. 55 ± 7 ng · μl-1, P < 0.05). The differences between control and L-NNA treated kidneys (with the exception of differences in FR(Gluc)) could be fully (L-NNA, 10 μM) or partially (L-NNA 100 μm) reversed by adding L-arginine (1 mM) to the perfusion medium. The observed results could be obtained in two different rat strains (Sprague-Dawley and Wistar). Only L-NNA and L-arginine caused the observed changes, while D-NNA and D-arginine were without effect. It is concluded that NO/EDRF is basally released from the isolated perfused rat kidney, and is of importance not only in the regulation of renal hemodynamics but also in the regulation of renal tubular function.