Prior Antagonism of Endothelin-1A Receptors Alleviates Circulatory Shock and Cerebral Ischemia During Rat Heatstroke

Journal of Pharmacological Sciences

Mao-Tsun Lin¹  Zhih-Cherng Chen²  Bor-Chih Cheng³  Chia-Chyuan Liu⁴ 

[1] Department of Medical Research, Chi-Mei Medical Center;Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center;Division of Cardiac Surgery, Department of Surgery, Chi-Mei Medical Center;Institute of Physiology, National Yang-Ming University Medical School

关键词: blood pressure;    cardiac output;    endothelin;    heatstroke;    receptor;   

DOI  :  10.1254/jphs.FP0040203

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(48)Cited-By(13)In this study, we investigated the acute hemodynamic effects of an infusion of the endothelin-1 (ET-1)-A-selective receptor antagonists BQ-610 and BQ-123 in heatstroke rats with circulatory shock and cerebral ischemia. Heatstroke was induced by putting the anesthetized adult Sprague-Dawley rats into an ambient temperature of 42°C. The moment in which the mean arterial pressure dropped irreversibly from the peak for an extent of 25 mmHg was taken as the onset of heatstroke. The interval between initiation of heat exposure and heatstroke onset was found to be about 80 min for rats treated with vehicle solution. When the animals were exposed to 42°C for 80 min, hyperthermia, arterial hypotension, decrement of cardiac output (due to decreased stroke volume and decreased total peripheral resistance), increment of plasma ET-1 and tumor necrosis factor-α, and increment of cerebral ischemia and injury markers were manifested. Prior antagonism of ET-1 A receptors with BQ-610 (0.5 mg/kg, i.v.) or BQ-123 (1 mg/kg, i.v.), but not ET-1B receptors with BQ-788 (0.5 mg/kg, i.v.), 60 min before the initiation of heat exposure, appreciably alleviated hyperthermia, arterial hypotension, decreased cardiac output, increment of tumor necrosis factor-α, and increment of cerebral ischemia (e.g., glutamate and lactate/pyruvate ratio) and injury (e.g., glycerol) markers exhibited during heatstroke. The data indicates that ET-1A receptor antagonism may maintain appropriate levels of mean arterial pressure and cerebral circulation during heatstroke by reducing production of tumor necrosis factor-α.

【 授权许可】

Unknown