Abstract

Objectives

Cigarette smoke, a strong risk factor for cardiovascular diseases, upregulates contractile endothelin (ET) receptors in coronary arteries. The present study examined the effects of second hand cigarette smoke exposure on the contractile endothelin receptors and the role of the MEK1/2 pathway in rat coronary arteries. Design: Rats were exposed to secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of a MEK1/2 inhibitor, U0126 daily for another 4 weeks. Contractile responses of isolated coronary arteries were recorded by a sensitive wire myograph. The receptor protein expression levels were examined by Western blotting. Results: The results showed that SHS in vivo caused increased expression of ET receptors ET_A and ET_B, and that the MEK1/2 blocker U0126 significantly reversed SHS exposure-increased ET_A-mediated contractile responses and protein levels. Similar alterations were observed in ET_B receptors. U0126 showed dose-dependent effects on SHS-induced response on contractile property and protein levels of the ET_B receptor. However, only the higher dose U0126 (15 mg/kg) had inhibitory effects on the ET_A receptor. Conclusions: Taken together, our data show that SHS increases contractile ET receptors and MEK1/2 pathway inhibitor offsets SHS exposure-induced ET_A and ET_B receptor upregulation in rat coronary arteries.

中文翻译：

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二手烟通过 MEK1/2 敏感机制诱导大鼠冠状动脉收缩性内皮素受体表达增加

摘要

目标

香烟烟雾是心血管疾病的重要危险因素，可上调冠状动脉中的收缩性内皮素 (ET) 受体。本研究调查了二手烟暴露对收缩性内皮素受体的影响以及 MEK1/2 通路在大鼠冠状动脉中的作用。设计：大鼠暴露于二手烟 (SHS) 8 周，然后腹腔注射 MEK1/2 抑制剂 U0126，每天持续 4 周。孤立的冠状动脉的收缩反应由灵敏的线肌描记器记录。通过蛋白质印迹检查受体蛋白表达水平。结果：结果表明，体内SHS引起ET受体ET _A表达增加_。和 ET _B，并且 MEK1/2 阻滞剂 U0126 显着逆转了 SHS 暴露增加的 ET _A介导的收缩反应和蛋白质水平。在ET _B受体中观察到类似的改变。U0126 对 SHS 诱导的 ET _B受体收缩特性和蛋白质水平的反应显示出剂量依赖性影响。然而，只有较高剂量U0126（15毫克/千克）对ET抑制作用_甲受体。结论：总的来说，我们的数据显示 SHS 增加收缩性 ET 受体，MEK1/2 通路抑制剂抵消了 SHS 暴露诱导的大鼠冠状动脉ET _A和 ET _B受体上调。