Naltrexone protects against hypotension, hyperthermia, and beta-endorphin overproduction during heatstroke in the rat.

Heat stroke is characterized by hyperthermia, arterial hypotension, decreased baroreflex sensitivity, and increased serum levels of beta-endorphin. Whereas naltrexone may have therapeutic potential in heat stroke, the underlying mechanism remains unclear. We tested the hypothesis that naltrexone may attenuate heat stroke by reducing hyperthermia, hypotension, decreased baroreceptor sensitivity, and/or increased serum levels of beta-endorphin. Heat stroke was induced by exposing the anesthetized adult Sprague-Dawley rats in an incubator at 43 degrees C. The moment in which the mean arterial pressure dropped irreversibly from the peak level was taken as the onset of heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure, baroreceptor sensitivity, and maximal reflex bradycardia, after the onset of heat stroke, were all significantly lower than in control rats. However, rectal temperature and serum levels of beta-endorphin were all greater after the onset of heat stroke. Intravenous delivery of naltrexone (10 mg/kg) 20 min before the initiation of heat stress, but not immediately at the onset of heat stroke, significantly attenuated the above-mentioned reactions. Accordingly, naltrexone improved survival during heat stroke. These results suggest that naltrexone protects against hypotension and decrement of both baroreceptor sensitivity and maximal reflex bradycardia during heat stroke by reducing both hyperthermia and increment of serum beta-endorphin and thus improves survival.