ER stress inhibition reduces cardiac damage and improves endothelial function in hypertensive mice

Abstract

Vascular complications and cardiac damage are major cause of mortality in hypertension. In this study we explored the beneficial effect of ER stress inhibition on vascular and cardiac damage in hypertensionMice were infused with Ang‐II with or without ER stress inhibitors (Tudca and PBA) for 2 weeks Mice infused with Ang‐II displayed an increase in SBP, cardiac hypertrophy and fibrosis associated with enhanced collagenI content, TGFb activity and ER stress markers which were blunted by ER stress inhibitors. AngII induced hypertension increased ER stress in aorta and mesenteric resistance arteries (MRA) enhanced TGFb activity in aorta but not in RA, reduced eNOS phosphorylation and endothelium‐dependent relaxation (EDR) in aorta and MRA. ER stress inhibition reduced TGFb fnactivity, enhanced eNOS phosphorylation and EDR. TGFb pathway inhibition improved EDR in aorta while the reduction in ROS levels ameliorated EDR in MRA onlyER stress inhibition reduces cardiac damage and improves vascular function in Ang II‐induced hypertension. ER stress could be a potential target for cardiovascular therapy