Xiamen Institute of Cardiovascular Diseases, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China.
Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen 361102, China.
Mediators Inflamm. 2019 Nov 14;2019:6248197. doi: 10.1155/2019/6248197. eCollection 2019.
During organ culture of intact vessels, endothelin receptors (ETRs) were upregulated in vascular smooth muscle cells (VSMCs) by various stimuli, but whether inflammation alters ETR expression in vivo remains unclear. We aimed to explore the effects of lipopolysaccharide (LPS) challenge on ETR expression in the VSMC in vivo. Male Sprague-Dawley rats received a single intraperitoneal injection of LPS (5 mg/kg body weight) or normal saline (NS) for 6 hrs. The function and expression of ETR type A (ET) and type B (ET) were evaluated in the mesenteric arteries without endothelium, by using myograph system, real-time quantitative PCR, Western blot, and immunohistochemical staining, respectively. Serum tumor necrosis factor- (TNF-) level was assessed by using enzyme-linked immunosorbent assay. The results showed that, compared to control (NS) group, LPS treatment potently enhanced the vasoconstriction mediated by ET or ET in rat mesenteric artery, with elevated maximum effects. ET and ET expressions in the VSMC were increased at both mRNA and protein levels after LPS treatment, paralleled with activation of the NF-B pathway and augmented serum TNF- level. Conclusively, in the rat model of immediate systemic inflammation induced by LPS, ET and ET expressions were increased in the mesenteric arterial VSMC, paralleled with enhanced receptor-mediated vasoconstriction and activation of the NF-B pathway. Our data has for the first time demonstrated the upregulation of ETRs in VSMCs by LPS-induced immediate inflammation in vivo.
在完整血管的器官培养中，各种刺激可使血管平滑肌细胞（VSMC）中的内皮素受体（ETR）上调，但炎症是否会改变体内的 ETR 表达尚不清楚。我们旨在探讨脂多糖（LPS）挑战对体内 VSMC 中 ETR 表达的影响。雄性 Sprague-Dawley 大鼠接受单次腹腔内注射 LPS（5mg/kg 体重）或生理盐水（NS）6 小时。通过使用肌动描记系统、实时定量 PCR、Western blot 和免疫组织化学染色，分别评估无内皮的肠系膜动脉中 ETR 型 A（ET）和型 B（ET）的功能和表达。通过酶联免疫吸附试验评估血清肿瘤坏死因子-（TNF-）水平。结果表明，与对照组（NS）相比，LPS 处理可显著增强大鼠肠系膜动脉中 ET 或 ET 介导的血管收缩作用，最大作用增强。LPS 处理后，VSMC 中 ET 和 ET 的表达在 mRNA 和蛋白水平上均增加，同时 NF-B 途径被激活，血清 TNF-水平升高。总之，在 LPS 诱导的即刻全身炎症的大鼠模型中，肠系膜动脉 VSMC 中 ET 和 ET 的表达增加，同时伴有受体介导的血管收缩增强和 NF-B 途径的激活。我们的数据首次证明了 LPS 诱导的体内即刻炎症可使 VSMC 中 ETR 上调。
