Effects of salicylate and 2,4-dinitrophenol on respiration and metabolism

The respiratory and metabolic responses to intravenous administration of sodium salicylate (240 mg/kg0.75) and 2,4-dinitrophenol (5.7 mg/kg0.75), uncouplers of oxidative phosphorylation, were studied in anesthetized, paralyzed, vagotomized, and glomectomized cats. During the initial 10 min after administration of salicylate, metabolic rate (VCO2) increased 70% and did not increase further during the experiment. Respiration, on the other hand, increased progressively at the same rate over the entire 60-min course of the experiment. The total increase in respiration was greater than 300%. Thus neither the time course nor the magnitude of the metabolic and respiratory responses were related. Similar findings were also obtained following administration of 2,4-dinitrophenol. We conclude that these agents stimulate respiration by a mechanism other than one related to the ability to uncouple oxidative phosphorylation and cause an increase in whole-body metabolism.