Abstract
Aim:
To investigate whether apocynin, a NADPH oxidase inhibitor, produced cardioproteictive effects in Ang II-induced hypertensive mice, and to elucidate the underlying mechanisms.
Methods:
C57BL/6 mice were subcutaneously infused Ang II for 4 weeks to mimic cardiac remodeling and fibrosis. Concomitantly the mice were administered apocynin (100 mg·kg−1·d−1) or/and the aldosterone receptor blocker eplerenone (200 mg·kg−1·d−1) via gavage for 4 weeks. Systolic blood pressure (SBP) and heart rate were measured, and transthoracic echocardiography was performed. For in vitro study, cardiac fibroblasts were treated with Ang II (10−7 mol/L) in the presence of apocynin (10−5 mol/L) or/and eplerenone (10−5 mol/L). Immunohistochemistry and Western blotting were used to quantify the expression levels of NADPH oxidase and osteopontin (OPN) proteins in the cells.
Results:
Both apocynin and eplerenone significantly decreased SBP, and markedly improved diastolic dysfunction in Ang II-induced hypertensive mice, accompanied with ameliorated oxidative stress and cardiac fibrosis. In the Ang II-treated cardiac fibroblasts, the expression levels of NOX4 and OPN proteins were markedly upregulated. Both Apocynin and eplerenone significantly suppressed the increased expression levels of NOX4 and OPN proteins in the Ang II-treated cells. In all the experiments, apocynin and eplerenone produced comparable effects. Co-administration of the two agents did not produce synergic effects.
Conclusion:
Apocynin produces cardioproteictive effects comparable to those of eplerenone. The beneficial effects of apocynin on myocardial oxidative stress and cardiac fibrosis might be mediated partly through a pathway involving NADPH oxidase and OPN.
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Acknowledgements
This work was supported by the Natural Science Foundation of Shanghai (11ZR1430500), the Science Fund of Shanghai Jiao Tong University School of Medicine (11XJ21034), the Shanghai Rising Star Program (11QA1405500), and the National Natural Science Foundation of China (30900808).
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Li, Yq., Li, Xb., Guo, Sj. et al. Apocynin attenuates oxidative stress and cardiac fibrosis in angiotensin II-induced cardiac diastolic dysfunction in mice. Acta Pharmacol Sin 34, 352–359 (2013). https://doi.org/10.1038/aps.2012.164
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DOI: https://doi.org/10.1038/aps.2012.164
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