Effect of furosemide on mitochondrial electron transport system and oxidative phosphorylation

The effects of furosemide on the mitochondrial electron transport system and on oxidative phosphorylation were explored. Furosemide above the concentration of 2 X 10(-3) mol/l was found to inhibit state 3 (ADP-dependent) respiration of the rat liver, renal cortex, renal medulla mitochondria. State 4 (resting) respiration was not affected by furosemide. Furosemide above the concentration of 7.5 X 10(-6) mol/l (substrate: glutamate-malate), and above 5 X 10(-6) mol/l (substrate: succinate) inhibited the respiration of rat liver mitochondria released by 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile (SF 6847). This fact exactly indicates that furosemide inhibits the electron transport system in mitochondria. Furosemide at the concentration of 4 X 10(-3) mol/l inhibited the activities of NADH cytochrome c reductase and succinate cytochrome c reductase in sonicated mitochondrial subparticles of beef heart by 78.2% and 79.2% of control, respectively.