Cerebrovascular dysfunction ensuing from severe
heatstroke includes
intracranial hypertension, cerebral hypoperfusion, and
brain inflammation. We attempted to assess whether
L-arginine improves survival during experimental
heatstroke by attenuating these reactions. Anesthetized rats, 70 min after the start of heat stress (43 degrees C), were divided into two major groups and given the following: vehicle
solution (1 mL/kg
body weight) or
L-arginine (50-250 mg/kg
body weight) intravenously. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat stress, their survival time values were found to be 20 to 26 min. Treatment with i.v. doses of
L-arginine significantly improved the survival rate during
heatstroke (54-245 min). As compared with those of normothermic controls, all vehicle-treated
heatstroke animals displayed higher levels of core temperature, intracranial pressure, and NO metabolite,
glutamate,
glycerol,
lactate-
pyruvate ratio, and
dihydroxybenzoic acid in hypothalamus. In addition, hypothalamic levels of IL-1beta and
TNF-alpha were elevated after
heatstroke onset. In contrast, all vehicle-treated
heatstroke animals had lower levels of MAP, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of
oxygen. Administration of
L-arginine immediately after the onset of
heatstroke significantly reduced the
intracranial hypertension and the increased levels of NO metabolite,
glutamate,
glycerol,
lactate-
pyruvate ratio, and
dihydroxybenzoic acid in the hypothalamus that occurred during
heatstroke. The
heatstroke-induced increased levels of IL-1beta and
TNF-alpha in the hypothalamus were suppressed by
L-arginine treatment. In contrast, the hypothalamic levels of
IL-10 were significantly elevated by
L-arginine during
heatstroke. The results suggest that
L-arginine may cause attenuation of
heatstroke by reducing cerebrovascular dysfunction and
brain inflammation.