Relative effects of furosemide and ethacrynic acid on ion transport and energy metabolism in slices of rat kidney-cortex

Summary

The effects of furosemide and ethacrynic acid have been studied using slices of rat kidney cortex incubated in a Ringer medium. At concentrations from 0.2–2.0 mM, furosemide had no significant effect on the tissue ATP content or on the metabolism-dependent net movements of intracellular Na⁺, K⁺ and Ca²⁺. It did, however, induce an increase in the net, outward movement of Cl⁻; we suggest that this may have srisen from inhibition of a Cl⁻ accumulating mechanism. In contrast, ethacrynic acid in the same concentration range caused marked reduction of cell respiration and ATP content and virtually total inhibitition of several processes of ion transport (Na⁺, Cl⁻ and Ca²⁺ loss, and K⁺ uptake). Concentrations of furosemide greater than 5 mM caused marked inhibition of energy metabolism and transport of ions, and 10 mM furosemide had quantitatively similar effects to 2 mM ethacrynic acid. Electron micrographs of kidney-cortex slices treated with the diuretics at 2 mM show that the ultrastructure was well maintained in the presence of furosemide but that ethacrynic acid caused severe structural disorganisation and necrosis. The mitochondria were generally in the orthodox configuration in the presence of furosemide, but swollen in ethacrynic acid in accord with the marked effects of 2 mM ethacrynate on mitochondrial energy metabolism. Of the effects we have detected, that of low concentrations of furosemide on Cl⁻ movement appears to be rather specific. Higher concentrations of this agent (5 mM and above), and all concentrations of ethacrynic acid studied (0.1–5.0 mM), have several inhibitory effects which seem to result from primary inhibition of mitochondrial activities and are presumably manifestations of toxicity.