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Cardiovascular Research Advance Access [Accepted Manuscript] published online on February 5, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn028
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Exercise training combined with angiotensin II receptor blockade limits post-infarct ventricular remodeling in rats

Xiaohua Xua, Wenhan Wana, Lisa Jib, Shunhua Laoa, Anthony S. Powersa, Weiyan Zhaoa, John M. Eriksonc and John Q. Zhanga,

a Laboratory of Cardiovascular Research, University of Texas at San Antonio, San Antonio, TX 78249 U.S.A.
b Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 U.S.A.
c Division of Cardiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 U.S.A.

Present address and address for correspondence: John Q. Zhang, Ph.D. Laboratory of Cardiovascular Research, University of Texas at San Antonio 1 UTSA Circle, San Antonio, TX 78249 U.S.A. Email: john.zhang{at}utsa.edu Phone: 1-210-458-7390 Fax: 1-210-458-5873

Aims: Our aim was to test the hypothesis that angiotensin II receptor blockade combined with exercise training after myocardial infarction (MI) could attenuate post-MI left ventricular remodeling and preserve cardiac function.

Methods: Sprague-Dawley rats underwent ligation of the left descending coronary artery, resulting in MI, or a sham operation. Losartan treatment and exercise training were initiated one week after infarction and continued for 8 weeks, either as a single intervention or combined.

Results: Collagen volume fraction in the sedentary MI (MISed) group was significantly higher than other MI groups treated with exercise training and/or losartan. Compared to MISed group, hearts of rats receiving exercise and/or losartan treatment had lower tissue inhibitor of matrix metalloproteinase (TIMP) 1. Matrix metalloproteinase (MMP) 2 or MMP-9 did not differ among all groups. Additionally, the level of angiotensin II receptor type 1 (AT1) protein significantly decreased in response to exercise training. Furthermore, angiotensin converting enzyme (ACE) binding was markedly lower in hearts receiving exercise training than in the MISed hearts. Cardiac function was preserved in rats receiving exercise training, and the beneficial effect was further improved by exercise combined with losartan treatment in comparison to the MISed group.

Conclusions: Our results suggest that post-MI exercise training and/or AngII receptor blockade reduces TIMP-1 expression and mitigates the expressions of ACE and AT1 receptor. These improvements, in turn, attenuate myocardial fibrosis and preserve post-MI cardiac function.

KEYWORDS myocardial infarction; remodeling; exercise; angiotensin; metalloproteinases

Time for primary review : 32


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