Section of Experimental Medicine, Department of Medicine, Georgia Regents University, Augusta, GA 30912, USA.
Am J Physiol Regul Integr Comp Physiol. 2013 Jul 15;305(2):R107-9. doi: 10.1152/ajpregu.00184.2013. Epub 2013 May 15.
Endothelin-1 (ET-1) is the most potent vasoconstrictor peptide known. It exerts its actions through two pharmacologically different receptors: ETA and ETB receptors. In the renal vasculature, there is a majority of ETB receptors in the efferent arteriole, whereas a greater amount of ETA receptors are located in the afferent arteriole. The nephron is rich in ETB receptors, especially in the thick ascending limb and collecting ducts, while containing a smaller amount of ETA receptors. High levels of circulating or renal ET-1 have been described in cardiovascular diseases such as hypertension or diabetes, diseases also associated to renal inflammation. Despite extensive evidence associating high levels of ET-1 to increased renal inflammation, the molecular mechanism(s) by which ET-1 leads to renal immune infiltration and/or immune activation remains unknown. In this minireview, we propose that the ET-1/ETA pathway mediates an increase in renal endoplasmic reticulum (ER) stress, initially a survival mechanism that if prolonged, leads to the eventual death of the cell via apoptosis.
内皮素-1（ET-1）是已知的最有效的血管收缩肽。它通过两种药理学上不同的受体发挥作用：ETA 和 ETB 受体。在肾血管中，大多数 ETB 受体位于出球小动脉，而更多的 ETA 受体位于入球小动脉。肾单位富含 ETB 受体，特别是在升支粗段和集合管中，同时含有较少的 ETA 受体。在心血管疾病如高血压或糖尿病等疾病中，循环或肾 ET-1 水平升高已被描述，这些疾病也与肾炎症有关。尽管有大量证据表明 ET-1 水平升高与肾炎症增加有关，但 ET-1 导致肾免疫浸润和/或免疫激活的分子机制尚不清楚。在这篇综述中，我们提出 ET-1/ETA 途径介导肾内质网（ER）应激的增加，最初是一种生存机制，如果持续时间延长，最终会通过细胞凋亡导致细胞死亡。
