MPS 07-07 INHIBITION OF ENDOPLASMIC RETICULUM STRESS IMPROVES CORONARY ARTERY FUNCTION IN THE SPONTANEOUSLY HYPERTENSIVE RATS

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Abstract

Objective:

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 SHRs.

Design and Method:

Sixteen-week old male SHRs and WKYs were treated with ER stress inhibitor (taurine-conjugated ursodeoxycholic acid, TUDCA, 100 mg/kg/day, IP injection) for two weeks. The systolic blood pressure, myogenic responses, and endothelium-dependent relaxation were measured. Western blot analysis was performed to measure changes in ER stress sensors and phosphorylation of 20 KDa myosin light chain (MLC20).

Results:

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 SHR, which were reduced by TUDCA treatment. Furthermore, phosphorylation of MLC20 was increased in SHR, which was reduced by the treatment of TUDCA.

Conclusions:

ER stress inhibition decreases systolic blood pressure and normalizes myogenic response and endothelium-dependent relaxation in SHR. Moreover, ER stress inhibition decreased MLC20 phosphorylation, which is associated with reduction of ER stress markers (Bip, ATF6, CHOP, IRE1, XBP1, PERK, and eIF2α). Therefore, we suggest that ER stress could be a potential target for hypertension.

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