Inhibition of endoplasmic reticulum stress improves coronary artery function in the spontaneously hypertensive rats

• DOI: 10.1038/srep31925
• Publication Date: 2016-08-23T09:38:12Z
• Authors: Soo-Kyoung Choi; Mihwa Lim; Seon-Hee Byeon; Young-Ho Lee
• Keywords: Male; Inbred SHR; Taurochenodeoxycholic Acid/pharmacology; Coronary Vessels/metabolism; Gene Expression Regulation/drug effects; 610; Biomarkers/metabolism; Rats, Inbred WKY; Coronary Vessels/physiopathology*; Article; Drug Administration Schedule; Taurochenodeoxycholic Acid; 03 medical and health sciences; Hypertension/metabolism; Rats, Inbred SHR; Animals; Inbred WKY; Phosphorylation; Taurochenodeoxycholic Acid/administration & dosage*; 0303 health sciences; Hypertension/physiopathology; Coronary Vessels/drug effects; Animal; Phosphorylation/drug effects; Endoplasmic Reticulum Stress; Coronary Vessels; Rats; Disease Models, Animal; Gene Expression Regulation; Disease Models; Hypertension; Endoplasmic Reticulum Stress/drug effects*; Biomarkers; Hypertension/drug therapy*

AbstractEndoplasmic 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 MLC20was 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.