| Summary: | 博士 === 國立陽明大學 === 生理學研究所 === 92 === In clinical situation, the patients with stroke, cerebral ischemia and trauma showed higher levels of endothelin-1 (ET-1) than normal subjects in plasma and cerebrospinal fluid. On the other hand, hydroxyethyl starch (HES) had beneficial effects in several cerebral ischemic models. The aim of the present study was to assess whether endothelin receptor antagonists pretreatment or HES treatment is able to attenuate both the arterial hypertension and cerebral ischemia exhibited during experimental heatstroke. In the present study, heatstroke was induced by putting the anesthetized adult rats to an ambient temperature of 42 ℃. The moment in which the mean arterial pressure dropped irreversibly from the peak was taken as the onset of heatstroke. When exposed animals to 42 ℃ for 80 min, hyperthermia, arterial hypotension, decrement of cardiac output (CO) (due to decreased stroke volume and decreased total peripheral resistance), increment of plasma ET-1 and tumor necrosis factor-alpha, and increment of cerebral ischemia and injury makers were manifested. Prior antagonism of endothelin tape A receptor (ETAR) with BQ-610 (0.5 mg/kg, i.v.), but not endothelin tape B receptor with BQ-788 (0.5 mg/kg, i.v.) 60 min before the initiation of heat exposure, appreciably alleviated hyperthermia, arterial hypotension, decreased CO, increment of tumor necrosis factor, and increment of cerebral ischemia and injury makers exhibited during heatstroke. In addition, the heatstroke-induced arterial hypotension, decreased stroke volume and total peripheral resistance, decreased blood pH and PaO2, decreased brain PO2, and increased levels of cerebral ischemia and injury markers were all attenuated significantly by increasing the volume expansion with 11 ml/kg of HES administered immediately at the onset of heatstroke. The data indicated that ETAR antagonist had a preventive effect, whereas HES therapy had a therapeutic effect during heatstroke.
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