Role of tissue hypermetabolism in stimulation of ventilation by dinitrophenol

Several authors have hypothesized that tissue hypermetabolism accounts for increases in ventilation (VE) elicited by 2,4-dinitrophenol. However, some data in the literature indicate that stimulation of VE by isomers of dinitrophenol is unrelated to tissue metabolic rate. To test this latter concept, we compared three different isomers of dinitrophenol (i.e., 2,4-dinitrophenol (2,4-DNP), 2,5-dinitrophenol (2,5,-DNP), 2,6-dinitrophenol (2,6-DNP) with respect to stimulation of VE and with respect to stimulation of oxygen consumption (VO2). In all experiments, 3-4 mg/kg of one dinitrophenol isomer was administered to chloralose anesthetized dogs by intra-arterial infusion. 2,4-DNP elicited large increments in both VE and VO2, 2,6-DNP elicited moderate increments in both VE and VO2, whereas 2,5-DNP elicited small increments in both VE and VO2. These observations demonstrate a correlation between ventilatory and metabolic changes affected by isomers of dinitrophenol. Accordingly, these results are consistent with the hypothesis that ventilatory stimulation by congeners of dinitrophenol is related to tissue hypermetabolism.