Losartan attenuates aortic endothelial apoptosis induced by chronic intermittent hypoxia partly via the phospholipase...

Endoplasmic reticulum (ER) stress is known to play key roles in the development of endothelial cell apoptosis induced by chronic intermittent hypoxia (CIH), and the angiotensin II-phospholipase C-inositol-1,4,5-triphosphate (AngII-PLC-IP3) pathway has been demonstrated to induce ER stress. To explore whether the AngII-PLC-IP3 pathway is involved in the vascular damage induced by CIH, we examined whether the AngII-PLC-IP3 pathway is involved in ER stress induced by CIH and whether losartan, a selective angiotensin II type 1 receptor (AT1R) blocker, could suppress endothelial cell apoptosis induced by CIH.

Adult male Sprague Dawley rats were subjected to 8 h/day of intermittent hypoxia/normoxia, with or without losartan, a selective AT1R blocker, and/or U73122, a selective PLC inhibitor, for 8 weeks. Endothelial cell apoptosis, ER stress markers, and levels of PLC-γ1 and IP3R expression were determined.

Losartan prevented increases in PLC-γ1 and IP3R protein levels and inhibited ER stress markers induced by CIH. Addition of U73122 reproduced all the protective effects of losartan. Losartan administration before CIH significantly ameliorated CIH-induced endothelial cell apoptosis.

This study showed that the AngII-PLC-IP3 pathway is involved in ER stress induced by CIH and that pre-losartan administration ameliorates endothelial cell apoptosis following CIH partly via inhibition of the AngII-PLC-IP3 pathway and ER stress.