In our previous study in guinea pigs, intensive and prolonged intraperitoneal heating (IPH) caused
heat stroke characterized by high mortality and accompanied by two paradoxical phenomena: ear skin vasoconstriction at a high body temperature (Tb) (
hyperthermia-induced vasoconstriction) and a post-IPH Tb fall at an ambient temperature (Ta) below thermoneutrality (
hyperthermia-induced hypothermia). In this study, we tested the hypothesis that the mechanisms of the two phenomena involve endogenous
opioid agonists. Experiments were conducted in 24 unanesthetized, lightly restrained guinea pigs, each chronically implanted with an intraperitoneal thermode and intrahypothalamic thermocouple. The thermoregulatory effects of a wide-spectrum
opioid-receptor antagonist,
naltrexone (NTX; 50 or 0 mumol/kg sc), were studied in IPH-induced
heat stroke and under normal conditions. IPH was accomplished by perfusing (50 ml/min; 80 min) water (45 degrees C) through the thermode. Ta was maintained at approximately 24 degrees C. Skin vasodilation occurred at the onset of IPH but later changed to vasoconstriction despite high Tb and continuing IPH. IPH-
induced hyperthermia (1.8 +/- 0.1 degrees C) was followed by a post-IPH Tb fall (-5.1 +/- 0.7 degree C; calculated for the survivors only). The 48-h mortality rate was 50%. NTX prevented the
hyperthermia-induced vasoconstriction and attenuated the
hyperthermia-induced hypothermia (-1.8 +/- 0.4 degree C). None of the NTX-treated animals died. The effects of NTX on Tb regulation under normal conditions were minor. These results indicate that the phenomena of both
hyperthermia-induced vasoconstriction and
hyperthermia-induced hypothermia are
opioid dependent. The latter is speculated to reflect
opioid-mediated inhibition of metabolism; the former is thought to result from
opioid-induced hemodynamic alterations. Because both phenomena did not occur in the NTX-treated survivors, the skin vasoconstriction at high Tb and the posthyperthermia Tb fall may be viewed as markers of the severity of
heat stroke. It is suggested that
opioid antagonists may have therapeutic potential in heat-induced disorders.