Involvement of Nitric Oxide in the Pathophysiology of Acute Heat Stress in the Rat

Abstract

The possibility that nitric oxide (NO) is involved in the pathophysiology of brain injury caused by heat stress (HS) was examined using immunohistochemistry of a constitutive isoform of neuronal nitric oxide synthase (c-NOS) in a rat model. In addition, to discover the role of oxidative stress in inducing c-NOS activity in HS, the effect of a new antioxidant H-290/51 on HS-induced expression of c-NOS immunoreactivity was examined. Subjection of conscious young animals to a 4-h HS in a biological oxygen demand (BOD) incubator at 38 degrees C resulted in marked upregulation of c-NOS in the cerebral cortex and hippocampus of stressed rats compared to normal rats kept at room temperature (21 +/- 1 degrees C). The c-NOS immunoreactivity was found in distorted neurons located in the edematous regions not normally showing c-NOS activity. Pretreatment with H-290/51 significantly attenuated the upregulation of c-NOS in animals subjected to HS, and the signs of neuronal distortion and edema were less pronounced. These results suggest that HS has the capacity to induce upregulation of c-NOS, and these effects can be reduced by prior treatment with H-290/51, indicating a possible neuroprotective effect of antioxidants in thermal brain injury.