Effect of Farosemide on Renal Glycolysis and Oxygen Uptake in Rats

Abstract

Furosemide (F), a potent diuretic agent, is known to inhibit tubular Na+ reabsorption. The mechanism of action of F is not known. Since Na+ reabsorption is energy dependent, F may inhibit this process by interference with renal energy metabolism. Normal, fed, 200 g sprague-Dawley male rats were used in this study. Homogenates of renal cortex and medulla were incubated in a medium containing 5 mM glucose (G). Addition of F (100–200 μg/ml) strongly inhibited formation of lactate (p<0.005), α-glycero-P (p<0.005), and all glycolytic intermediates below 1,3-diP-glycyerate (p<0.005) in both tissues; fructose-6-P increased sharply; triose-P formation did not change. The QO2 of renal cortex and medulla slices obtained from controls, or 1 h after IV injection of F (20 mg/kg), were measured in a Warburg respirometer. Endogenous QO2 was increased in the F-group cortex and medulla (p<0.02); addition of G (5 mM) enhanced QO2 in control cortex and medulla (p<0.005) but not in F-group cortex. However, in F-group medulla, a synergistic effect of F+G on enhancement of QO2 was observed. Decreased lactate formation from G is consistent with inhibited glycolysis or enhanced krebs cycle activity; our data indicate both may play a role. Inhibition of glycolysis may be a direct effect of F, or may result from increased Krebs cycle activity [News-Holme et al., Nature 193: 270, 1962]. The increased CO2 with F in renal slices suggests uncoupling of the usual relationship between Na+ reabsorption and renal O2 utilization.