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Heart rate reduction in middle‐aged post‐MI rats attenuates the renin‐angiotensin system, prevents periarteriolar fibrosis and improves myocardial perfusion
Author(s) -
Dedkov Eduard I,
Zheng Wei,
Christensen Lance P,
Weiss Robert M,
MahlbergGaudin Florence,
Tomanek Robert J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a973-a
Subject(s) - medicine , perfusion , myocardial fibrosis , cardiology , endocrinology , fibrosis , muscle hypertrophy , myocardial infarction
We tested the hypothesis that heart rate reduction induced in middle‐aged post‐MI rats can improve perfusion in the surviving LV myocardium by attenuating periarteriolar fibrosis. MI was induced in 12‐month‐old Sprague‐Dawley rats, which were then treated either with ivabradine (MI+IVA) or placebo (MI) via osmotic pumps for 4 weeks. In addition, blood and tissue samples were obtained at 3, 7 and 14 days after MI. Four weeks of IVA treatment did not affect infarct size, cardiac hypertrophy, arteriolar or capillary growth. However, perivascular collagen content in MI+IVA rats was 37% and 40% lower in the LV free wall and septum, respectively, and was associated with greater (26%) maximal myocardial perfusion. Tissue expression of ANG II type 1 receptor and TGFβ 1 proteins, as well as the plasma level of ANG II peptide, were higher in untreated compared to IVA‐treated rats 14 days after MI. Thus, the data indicate that improved myocardial perfusion in MI+IVA rats was the result of the lower periarteriolar collagen content rather than to arteriolar growth. We suggest that an inhibition of the RAS may be a mechanism by which IVA‐induced heart rate reduction affects the myocardial collagen of post‐MI rats. Supported by IRI Servier.