Substrate support for renal functions during hypoxia in the perfused rat kidney

Abstract

Do the substrates that can be utilized for anaerobic ATP production by cytosolic (G, glycolytic) and/or mitochondrial (M) metabolic pathways support renal function during marked hypoxia? The isolated rat kidney was perfused at 38 degrees C, pH 7.4, at a mean pressure of 120 mmHg for 110 min with a Krebs-Ringer bicarbonate solution containing 6 g/100 ml substrate-free albumin (SFA0). After substrate-free aerobic (PO2 = approximately 646 mmHg) internal control observations were made, the perfusate was gassed with 95% N2/5% CO2 (n = 15) and substrates (each 5 mM) were added (G, glucose, K, alpha-ketoglutarate, A, aspartate), or SFA0 perfusion was continued. Perfusion flow rate (PFR) increased 20-43% during hypoxia; thus there was no limitation in substrate delivery to the kidney. Although GFR decreased during all hypoxic perfusions, due to the variations in GFR, the reductions in GFR were not significant. Fractional Na+ reabsorption (%TNa+) was reduced in the hypoxic kidney but the decreases in %TNa+ in the presence of G or M substrates were significantly smaller (-26 to -36%) than the decreases observed during hypoxic SFA0 perfusion (-44%). Free water clearance decreased markedly during substrate-free hypoxic perfusion; by contrast, addition of G or M substrates either increased or maintained CH2O. G increased hypoxic CH2O (+194% to +440% of internal control) more than did M substrates. It is postulated that the increases in %TNa+ in the presence of substrates during hypoxia results in the increases in GFR. By making substrates available that can be oxidized anaerobically in cytosol or in mitochondria, the kidney can better maintain a portion of its tubular functions during severe hypoxia.