L-arginine causes amelioration of cerebrovascular dysfunction and brain inflammation during experimental heatstroke.

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.