Telmisartan protects chronic intermittent hypoxic mice via modulating cardiac renin-angiotensin system activity

Wanyu Wang,Yiming Zeng,Ailing Song,Yixiang Zhang,Yonghong Shi,Wen Luo,Xiaoyang Chen,Yihua Lin

doi:10.1186/s12872-018-0875-4

Abstract

BackgroundTo explore the effects of chronic intermittent hypoxia (CIH), which mimics sleep apnea syndrome, on the cardiac renin angiotensin system (RAS), and to investigate the cardiac protection of an angiotensin receptor blocker (ARB)telmisartan (TERT) against CIH.Methods32 healthy male C57B6J mice were randomly divided into CIH, ARB, blank and air control groups. CIH lasted for 12 weeks. Cardiac angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE 2) and angiotensin II (Ang II) were evaluated by immunohistochemistry. Myocardial apoptosis were assessed by TUNEL assay and myocardial cell ultrastructure were observed under transmission electron microscope.ResultsCardiac ACE expression was higher in the CIH group than in blank and air control groups, which was decreased with TERT treatment. TERT treatment elevated the expression of cardiac ACE 2 and Ang II compared with CIH group. Myocardial cell and capillary endothelial cell apoptosis, mitochondrial injury were most severe in CIH groups, which were mitigated with TERT treatment.ConclusionsCIH changes the expression of cardiac ACE, ACE2 and Ang II, which may cause myocardial damage. TERT protects mice from CIH-linked cardiac damage via modulating the activity of RAS in the hearts.

Highlights

To explore the effects of chronic intermittent hypoxia (CIH), which mimics sleep apnea syndrome, on the cardiac renin angiotensin system (RAS), and to investigate the cardiac protection of an angiotensin receptor blocker (ARB)telmisartan (TERT) against CIH
TERT treatment reduced the level of angiotensin converting enzyme (ACE), this reduction did not reach statistical significance compared with the CIH group
In the myocardium of the apex of the heart, Ang angiotensin II (II) staining was mainly localized in the cytoplasm (Fig. 2a-h), and its expression was higher in CIH group than in blank and air control groups (#p < 0.05 vs two control groups)

Summary

Introduction

To explore the effects of chronic intermittent hypoxia (CIH), which mimics sleep apnea syndrome, on the cardiac renin angiotensin system (RAS), and to investigate the cardiac protection of an angiotensin receptor blocker (ARB)telmisartan (TERT) against CIH. Chronic intermittent hypoxia (CIH) is one of the distinctive pathophysiological features of SAS, and is implicated in the development of SAS-associated CVDs. One of the mechanisms by which CIH promotes CVDs is the activation of the renin-angiotensin system (RAS) [2], a well-known contributor to the pathogenesis of CVDs. a key component of RAS, angiotensin converting enzyme 2 (ACE 2), inhibits RAS and exhibits. We explored whether TERT could protect against CIH-induced cardiac damage via modulating the activity of the RAS. Our goal was to elucidate the mechanisms by which TERT, and more generally, ARB, may act in the treatment of SAS

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