Inhibition of Endoplasmic Reticulum Stress Normalizes Augmented Myogenic Response in Coronary Arteris of the Spontaneously Hypertensive Rats

Abstract

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). We investigated this hypothesis by suppressing ER stress in SHRs and their normotensive controls, Wistar‐Kyoto rats (WKYs) with ER stress inhibitor (taurine‐conjugated ursodeoxycholic acid, TUDCA). Sixteen‐week old male SHRs and WKYs were treated with TUDCA (100 mg/kg/day, IP injection) or PBS (control, 300 μl/day, IP injection) for two weeks. There was a decrease in systolic blood pressure in SHR treated with TUDCA but not in SHR treated with PBS. The myogenic response is potentiated in coronary arteries of SHRs compared to WKYs. Interestingly, treatment of ER stress inhibitor normalized myogenic responses in SHRs. These data were associated with an increase in ER stress marker expression (Bip, CHOP, ATF6, XBP‐1, and phosphorylated‐eIF2α) in coronary arteries of SHRs, which were reduced by TUDCA treatment. In conclusion, ER stress inhibition decreases systolic blood pressure and normalizes myogenic response in SHRs. Moreover, ER stress inhibition reduces expression of ER stress markers. Therefore, we suggest that ER stress could be a potential target for hypertension.