Angiotensin II and endothelin‐1 induce endoplasmic reticulum stress in aortic vascular smooth muscle cells

Angiotensin II (AngII) and endothelin‐1 (ET‐1) play a role in the pathology of hypertension and both cause oxidative stress. Evidence has shown a link between oxidative stress and endoplasmic reticulum (ER) stress. ER stress is an emerging mechanism in several metabolic and cardiovascular diseases, but its role in hypertension remains unclear. We hypothesize that AngII and ET‐1 cause ER stress in vascular smooth muscle cells (VSMCs). Protein expression of 3 major ER stress markers was measured (Grp‐78, ATF6, and CHOP) from cultured male Wistar rat aortic VSMCs treated with AngII or ET‐1(10nm, 24 hours, DMEM, n=6). Grp‐78, an ER chaperone, which gets upregulated during ER stress, was significantly increased in VSMCs following treatment with Ang II or ET‐1. ATF6 is an ER transmembrane protein that gets cleaved from a 90kDa protein to a 50 kDa protein during ER stress. We found that the expression of the 50 kDa protein was significantly elevated in VSMC following treatment with Ang II or ET‐1. CHOP is a pro‐apoptotic protein that is over expressed after a cell undergoes prolonged ER stress. We observed that CHOP was not significantly upregulated after treatment with Ang II or ET‐1, showing VSMCs are able to survive ER stress during 24hr treatment. We conclude that Ang II and ET‐1 induce ER stress in VSMCS. Alterations in these ER stress proteins may contribute to vascular dysfunction in hypertension.