Effect of 2,4-dinitrophenol on the hypometabolic response to hypoxia of conscious adult rats.
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 O2 availability, pharmacological uncoupling of the oxidative phosphorylation should raise O2 consumption (VO2) 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), VO2, as measured by an open-flow technique, was less than in normoxia (approximately 80%). Successive DNP injections (6 mg/kg, 4 times) progressively increased VO2 in both normoxia and hypoxia by similar amounts. Body temperature slightly increased in normoxia, whereas it did not change in hypoxia. The DNP-stimulated VO2 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 of VO2 counteracts the VO2 drop determined by hypoxia and stimulates VO2 not dissimilarly from normoxia. Hypoxic hypometabolism is likely to reflect a regulated process of depression of thermogenesis, with no limitation in cellular O2 availability.
Saiki
C
C
Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Mortola
J P
JP
D019297:2,4-Dinitrophenol / Q000494:pharmacology*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects; D000860:Hypoxia / Q000378:metabolism*; D007267:Injections; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D014475:Uncoupling Agents / Q000494:pharmacology*
D014475:Uncoupling Agents; D019297:2,4-Dinitrophenol