Inhibition of endoplasmic reticulum stress improves coronary artery function in the spontaneously hypertensive rats.
Inhibition of endoplasmic reticulum stress improves coronary artery function in the spontaneously hypertensive rats.
复制标题
DOI：
10.1038/srep31925
复制
发表时间：
2016-08-23
影响因子：
4.6
通讯作者：
Lee YH
中科院分区：
文献类型：
--
作者：
Choi SK;Lim M;Byeon SH;Lee YH
内质网（ER）应激在心血管并发症的发病机制中起重要作用。然而，ER应激在高血压中的作用和机制尚不清楚。因此，我们假设增强ER应激有助于维持自发性高血压大鼠（SHR）的高血压。本研究使用16周龄雄性SHR和Wistar京都大鼠（WKY）。用ER应激抑制剂（牛磺熊去氧胆酸; TUDCA，100 mg/kg/天）处理SHR两周。TUDCA处理的SHR收缩压降低。与WHY相比，SHR的压力诱导的肌源性张力显著增加，而内皮依赖性舒张显著减弱。有趣的是，ER应激抑制剂治疗使SHR的生肌反应和内皮依赖性舒张正常化。这些数据与SHR中ER应激标志物（Bip、ATF 6、CHOP、IRE 1、XBP 1、PERK和eIF 2 α）的表达或磷酸化增加相关，而TUDCA处理降低了这些表达或磷酸化。此外，MLC 20的磷酸化在SHR中增加，TUDCA处理降低。因此，我们的结果表明ER应激可能是高血压的潜在目标。
Endoplasmic reticulum (ER) stress has been shown to play a critical role in the pathogenesis of cardiovascular complications. However, the role and mechanisms of ER stress in hypertension remain unclear. Thus, we hypothesized that enhanced ER stress contributes to the maintenance of hypertension in spontaneously hypertensive rats (SHRs). Sixteen-week old male SHRs and Wistar Kyoto Rats (WKYs) were used in this study. The SHRs were treated with ER stress inhibitor (Tauroursodeoxycholic acid; TUDCA, 100 mg/kg/day) for two weeks. There was a decrease in systolic blood pressure in SHR treated with TUDCA. The pressure-induced myogenic tone was significantly increased, whereas endothelium-dependent relaxation was significantly attenuated in SHR compared with WHY. Interestingly, treatment of ER stress inhibitor normalized myogenic responses and endothelium-dependent relaxation in SHR. These data were associated with an increase in expression or phosphorylation of ER stress markers (Bip, ATF6, CHOP, IRE1, XBP1, PERK, and eIF2α) in SHRs, which were reduced by TUDCA treatment. Furthermore, phosphorylation of MLC20 was increased in SHRs, which was reduced by the treatment of TUDCA. Therefore, our results suggest that ER stress could be a potential target for hypertension.