Renal energy metabolism and sodium reabsorption after 2,4-dinitrophenol administration

2,4-Dinitrophenol (DNP) (10 mg/kg body wt i.v.) increased renal cortical and outer medullary heat production rates and oxygen consumption by 70-90% in anesthetized dogs over a 90-min observation period without exerting any natriuretic effect. To examine whether DNP inhibited proximal reabsorption and increased distal delivery, ethacrynic acid (3 mg/kg body wt) was infused during maximal DNP effect. Sodium reabsorption fell by 14 +/- 6% in the cortex and 55 +/- 8% in the outer medulla, not significantly different from control experiments without DNP. Conversely, after ethacrynic acid administration, DNP had no additional natriuretic effect. Since DNP did not stimulate renal anaerobic metabolism (no lactate release), the effect of DNP was examined during hypoxia induced by intravenous infusion of NaCN (0.2 mumol/kg body wt-min) until renal metabolic rates fell. Subsequent infusion of DNP reduced tubular sodium reabsorption from 90 +/- 2 to 78 +/- 6%. Thus, DNP may raise renal metabolic rates by 70-90% without inhibiting sodium reabsorption, but, under conditions of hypoxia, DNP reduces sodium reabsorption and increases sodium excretion.