Effect of 2,4-dinitrophenol on the hypometabolic response to hypoxia of conscious adult rats

Abstract

Saiki, Chikako, and Jacopo P. Mortola. Effect of 2,4-dinitrophenol on the hypometabolic response to hypoxia of conscious adult rats. J. Appl. Physiol. 83(2): 537–542, 1997.—During acute hypoxia, a hypometabolic response is commonly observed in many newborn and adult mammalian species. We hypothesized that, if hypoxic hypometabolism were entirely a regulated response with no limitation in O2availability, pharmacological uncoupling of the oxidative phosphorylation should raise O2consumption (V˙o 2) by similar amounts in hypoxia and normoxia. Metabolic, ventilatory, and cardiovascular measurements were collected from conscious rats in air and in hypoxia, both before and after intravenous injection of the mitochondrial uncoupler 2,4-dinitrophenol (DNP). In hypoxia (10% O2 breathing, 60% arterial O2 saturation),V˙o 2, as measured by an open-flow technique, was less than in normoxia (∼80%). Successive DNP injections (6 mg/kg, 4 times) progressively increasedV˙o 2 in both normoxia and hypoxia by similar amounts. Body temperature slightly increased in normoxia, whereas it did not change in hypoxia. The DNP-stimulatedV˙o 2 during hypoxia could even exceed the control normoxic value. A single DNP injection (17 mg/kg iv) had a similar metabolic effect; it also resulted in hypotension and a drop in systemic vascular resistance. We conclude that pharmacological stimulation ofV˙o 2 counteracts theV˙o 2 drop determined by hypoxia and stimulates V˙o 2not dissimilarly from normoxia. Hypoxic hypometabolism is likely to reflect a regulated process of depression of thermogenesis, with no limitation in cellular O2availability.