Angiotensin II receptor blocker irbesartan attenuates sleep apnea-induced cardiac apoptosis and enhances cardiac survival and Sirtuin 1 upregulation.

Abstract

BACKGROUND:

The purpose of this study was to investigate whether or not angiotensin II type 1 receptor blocker irbesartan (ARB) with a partial agonist of PPAR-γ could protect against chronic nocturnal intermittent hypoxia (CIH)-induced cardiac Fas/FasL-mediated to mitochondria-mediated apoptosis.

METHODS:

Sprague-Dawley rats were in a normoxic control group (CON-G), or rats were in a chronic nocturnal intermittent hypoxia group (HP-G, from 3 to 7% oxygen versus 21% oxygen per forty seconds cycle, nocturnally 8 h per day for 1 month), or rats were in a chronic nocturnal intermittent hypoxia group pretreated with ARB (50 mg/kg/day, S.C.) (ARB-HP-G). Echocardiography, H&E staining, TUNEL staining, and Western blotting were measured in the left ventricle.

RESULTS:

Hypoxia-induced SIRT1 degradation, Fas receptors, FADD, active caspase-8 and caspase-3 (Fas/FasL apoptotic pathway) and Bax, tBid, active caspase-9 and -3 (mitochondrial apoptotic pathway) and TUNEL-positive apoptosis were reduced in ARB-HP-G when compared with HP-G. IGF-I, IGF1 receptor, p-PI3k, p-Akt, Bcl2, and Bcl-XL (IGF1/PI3K/AKT pro-survival pathway) were increased in ARB-HP-G compared to HP-G.

CONCLUSIONS:

Our findings suggest that the ARB may prevent cardiac Fas/FasL to mitochondrial apoptotic pathways and enhance cardiac IGF1/PI3K/AKT pro-survival pathway in the sleep apnea model associated with JNK de-activation and SIRT1 upregulation. ARB prevents chronic sleep apnea-enhanced cardiac apoptosis via enhancing survival pathways.

• Authors: Pei-Ying Pai, Yi-Yuan Lin, Shao-Hong Yu, Ching-Yuang Lin, Yi-Fan Liou, Xu-Bo Wu, James K S Wong, Chih-Yang Huang, Shin-Da Lee
• Journal: Sleep & breathing = Schlaf & Atmung (Sleep Breath) Vol. 26 Issue 3 Pg. 1161-1172 (09 2022) ISSN: 1522-1709 [Electronic] Germany
• PMID: 34626328 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Proto-Oncogene Proteins c-akt
• Sirtuin 1
• Irbesartan
• Oxygen

Topics

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Animals
• Apoptosis
• Hypoxia
• Irbesartan
• Myocardium
• Oxygen
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Rats
• Rats, Sprague-Dawley
• Sirtuin 1
• Sleep Apnea Syndromes
• Up-Regulation