Cholinergic drug interactions and heat tolerance

Abstract

Acute, subchronic and chronic exposures to cholinergic compounds may result in differing effects. The efficacy of pyridostigmine bromide (PY) prophylaxis against organophosphorus poisoning depends on post exposure atropine (AT) administration. AT induces a dose-dependent increase in rate of rise of core temperature in heat exposed humans and rats. To determine whether AT's anticholinergic potency is altered following PY administration, we examined AT's effects following acute or subchronic (2 weeks) PY administration in the sedentary heat-stressed rat. Four groups of rats were acutely (a,iv) treated with saline (SAL) or PY (100 ug/kg) followed by SAL or AT (200 ug/kg), and 4 groups were subchronically (c, osmotic pump) treated with SAL or PY (20 ug/hr) followed by SAL or AT (200 ug/kg). Fifteen minutes following the final injection, rats were subjected to an ambient temperature of 41.5°C until a core temperature of 42.6°C was attained. Heat tolerance times were significantly improved for cPY+SAL over aPY+SAL (241 ± 9 vs 187 ± 16 min, mean ± SE) and for cPY+AT over aPY+AT (76 ± 9 vs 57 ± 2 min). The improvement in thermoregulation resulted from increased salivary water for evaporative cooling indicated by % weight loss (corrected for fecal loss) during heat stress: cPY+SAL over aPY+SAL (8.4 ± 0.3 vs 6.6 ± 0.5%). This increased heat tolerance resulting from subchronic anticholinesterase administration resembles changes seen with heat acclimation.