MECHANISMS OF THERMAL RESPONSES TO 2,4-DINITROPHENOL

¹ Department of Pharmacology and Therapeutics, University of Manitoba Faculty of Medicine, Winnipeg, Manitoba, Canada

2,4-Dinitrophenol (DNP) produced a consistent hyperthermia in lightly restrained rats at ambient temperatures above 20 to 22°C, and a hypothermia at lower ambient temperatures. DNP failed to affect body temperature in curarized rats at a low ambient temperature. DNP produced a smaller increase in oxygen consumption of lightly restrained rats at lower ambient temperatures.

In contrast to its effects in rats, DNP in doses of 3.0 and 20 mg/kg did not affect the body temperature of lightly restrained dogs at low ambient temperatures (10 and 4°C). Visible shivering was not noticeably influenced by the dose of 3.0 mg/kg but was greatly diminished by 20 mg/kg. A relative hyperthermia was produced in dogs completely paralyzed with a neuromuscular blocking agent at all ambient temperatures studied (5 to 20°C). The hyperthermia was due to increased heat production which was not significantly different at different ambient temperatures.

Intracarotid infusion of a small dose of DNP in "curarized" dogs over a 10-minute period produced a much smaller increase in oxygen consumption than did intravenous infusion of the same dose.

These results indicate that the hypothermic effect of DNP probably is due to both a centrally-mediated inhibition of the skeletal muscle thermogenic response to cold and to a reduced metabolic effect of DNP at low ambient temperatures. The hyperthermic effect of DNP, on the other hand, probably can be attributed entirely to a peripherally-mediated thermogenic action.