Effects of Administration with BQ 788 on Heat Stroke in Rats

Abstract

Heat stroke was induced by placing urethane-anesthetized rats in the hot chamber with 42℃ ambient temperature. Instead, the normothermic control rats were placed in chamber with room temperature, 24℃. The onset of the rapidly decreased mean arterial pressure (MAP) and cerebral blood flow (CBF) from peak level was defined as the onset of heat stroke. And the interval from the onset of heat stroke to cardiac arrest was defined as the survival time (ST) of rats. The values of MAP and CBF after heat stroke onset were significantly lower than those in control rats. However, plasma levels of tumor necrosis factor-α (TNF-α) were higher. Extracellular concentration of glutamate and lactate/pyruvate ratio (cellular ischemia markers), and glycerol (a cellular injury marker) in the corpus striatum were markedly greater. The role of ET-1 in the pathological manifestations of heat stroke is worth further study. Effects following endothelin B (ETB) receptor activation (but not ETA receptor) by ET-1 on cytokine production of human monocytes with 7-fold higher release of TNF-α, compared to another cytokines. There were sufficient evidences to show that high levels of TNF-α not only resulted multi-organ dysfunction via inflammatory response and led to shorten the survival time of heat stroke animals, but were closely associated with cardiac function in various cardiovascular disorders. Additionally, there was less attention to clarify in detail the effective on heat stroke with ETBR antagonists. Therefore, in present study, we attempted to investigate effects of acute treatment or pretreatment with an ETBR antagonist (BQ 788) on heat stroke-induced pathophysiologic changes (including arterial hypotension, cerebral ischemia, and neuronal damage) and survival in a rat model. In present study, our results suggest that heat stroke induced low SBF, high levels of plasma TNF-α, arterial hypotension, cerebral ischemia, neuronal damage, and a decrease in survival time in rats. We tried to give BQ 788 immediately or beforehand, and expect to be able to improve the heat stroke-induced arterial hypotension, cerebral ischemia, and neuronal damage, and eventually resulted in prolongation of the survival time; however, ETBR antagonist, showed no efficacy in those lesions and symptoms. Our investigations implicate that the pretreatment or treatment with ETBR may have no efficiency to diminish the damage and pathological formation of heat stroke in a rat model.