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

Abstract

PURPOSE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Jie Ren, Wei Liu, Yan Deng, Guang-Cai Li, Yue-Ying Pan, Sheng Xie, Meng Jin, Hui-Guo Liu
• Journal: Sleep & breathing = Schlaf & Atmung (Sleep Breath) Vol. 21 Issue 3 Pg. 679-689 (Sep 2017) ISSN: 1522-1709 [Electronic] Germany
• PMID: 28190165 (Publication Type: Journal Article)

Chemical References

• Type C Phospholipases
• Losartan

Topics

• Animals
• Aorta (cytology)
• Apoptosis (drug effects)
• Endothelial Cells (cytology, drug effects, enzymology, metabolism)
• Hypoxia (complications)
• Losartan (pharmacology)
• Male
• Rats
• Rats, Sprague-Dawley
• Type C Phospholipases (metabolism)