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Apocynin attenuates oxidative stress and cardiac fibrosis in angiotensin II-induced cardiac diastolic dysfunction in mice.
MedLine Citation:
PMID:  23334241     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Yu-Qiong Li; Xiao-Bo Li; Shu-Jie Guo; Shao-Li Chu; Ping-Jin Gao; Ding-Liang Zhu; Wen-Quan Niu; Nan Jia
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-21
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  -     ISSN:  1745-7254     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China [2] Shanghai Institute of Hypertension, Shanghai 200025, China [3] State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
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