Original Article

Apocynin attenuates oxidative stress and cardiac fibrosis in angiotensin II-induced cardiac diastolic dysfunction in mice

Authors: Yu-qiong Li, Xiao-bo Li, Shu-jie Guo, Shao-li Chu, Ping-jin Gao, Ding-liang Zhu, Wen-quan Niu, Nan Jia
DOI: 10.1038/aps.2012.164


Wei SHI1, 2, *, J Gary MESZAROS3, Shao-ju ZENG1, Ying-yu SUN1, Ming-xue ZUO1, *
Laboratory of Neuroscience and Brain Development, School of Life Science, Beijing Normal University, Beijing 100875, China; 2School of Biomedical Sciences, Kent State University, Kent, OH 44240, USA; 3Department of Integrative Medical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH 44272, USA

Aim: Living high training low” (LHTL) is an exercise-training protocol that refers living in hypoxia stress and training at normal level of O2. In this study, we investigated whether LHTL caused physiological heart hypertrophy accompanied by changes of biomarkers in renin-angiotensin system in rats.

Methods: Adult male SD rats were randomly assigned into 4 groups, and trained on living low-sedentary (LLS, control), living low-training low (LLTL), living high-sedentary (LHS) and living high-training low (LHTL) protocols, respectively, for 4 weeks. Hematological parameters, hemodynamic measurement, heart hypertrophy and plasma angiotensin II (Ang II) level of the rats were measured. The gene and protein expression of angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II receptor I (AT1) in heart tissue was assessed using RT-PCR and immunohistochemistry, respectively.

Results: LLTL, LHS and LHTL significantly improved cardiac function, increased hemoglobin concentration and RBC. At the molecular level, LLTL, LHS and LHTL significantly decreased the expression of ACE, AGT and AT1 genes, but increased the expression of ACE and AT1 proteins in heart tissue. Moreover, ACE and AT1 protein expression was significantly increased in the endocardium, but unchanged in the epicardium.

Conclusion: LHTL training protocol suppresses ACE, AGT and AT1 gene expression in heart tissue, but increases ACE and AT1 protein expression specifically in the endocardium, suggesting that the physiological heart hypertrophy induced by LHTL is regulated by region-specific expression of renin-angiotensin system components.

Keywords: exercise-training; living high training low; hypoxia stress; heart hypertrophy; renin-angiotensin system; angiotensin-converting enzyme; angiotensin II receptor; cardiac function

This work was supported by grants from the National Natural Science Foundation of China (No 30870307) and the Beijing Natural Science Foundation of China (No 5092013) to Ming-xue ZUO. Also, the first author’s parents and the China Education Department supported part of this work as an undergraduate student research fellowship. The authors gratefully thank Prof Xiao-li LIU, Associate Prof Qiu-yun LIU, William HAMLET and Dr Yong LU for the technical assistance and helpful review of the manuscript.
* To whom correspondence should be addressed.
E-mail mxzuo@bnu.edu.cn (Ming-xue ZUO); shiweiphd@gmail.com (Wei SHI)
Received 2012-07-05 Accepted 2012-11-28

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