Osmotic thirst suppression during 2,4-dinitrophenol (DNP) hyperthermia in the dog

Abstract

The effect of generalized body hyperthermia elicited by intravenous infusion of 2,4-dinitrophenol (DNP) on the reactivity of the thirst mechanism to osmotic stimuli was examined in conscious dogs. DNP increased deep body temperature by 1.53 +/- 0.18 degrees C in 18 out of 20 experiments. Impairement of thrist sensation was observed at the same time. The animals did not drink enough water to compensat for its total and evaporative loss. In cosequence water deficit developed, reaching maximum value of 2.7 plus 0.6% of body weight. The deficit was accompanied by an increase in plasma osmolarity, plasma protein concentration and hematocrit. A significant correlation between evaporative water loss and water deficit as well as between increase in deep body temperature and water deficit was found. The cellular dehydration developed in the course of DNP hyperthermia was higher by 3.3 +/- 0.6% of intracellular water (P less than 0.001) than that which was necessary to elicit drinking under conditions of normothermia. It is concluded that DNP hyperthermia changes the osmotic reactivity of the thirst mechanism so that the body fluids osmolarity is regulated at a higher level. This finding is discussed with regard to voluntary dehydration.

Evaluation of efficacy of resin hemoperfusion in patients with acute 2,4-dinitrophenol poisoning by dynamic monitoring of plasma toxin concentration

“…The major route of 2,4-DNP metabolism is through the liver, and most metabolites are excreted in the urine together with prototypical 2,4-DNP. Data for the pharmacokinetics of 2,4-DNP in animal models vary greatly (Szczepańska-Sadowska, 1975;Phillips and Singer, 2013). There are no reliable data to define the pharmacokinetics of 2,4-DNP in humans.…”