Article date: February 2001
By: Steffen Sandmann, Minghuan Yu, Thomas Unger in Volume 132, Issue 3, pages 767-777
Recent studies demonstrated that the cardiac calpain system is activated during ischaemic events and is involved in cardiomyocyte injury. The aim of this study was to investigate the contribution of AT1 and AT2 receptors in the regulation of calpain‐mediated myocardial damage following myocardial infarction (MI).
Infarcted animals were treated either with placebo, the ACE inhibitor ramipril (1 mg kg−1 d−1), the AT1 receptor antagonist valsartan (10 mg kg−1 d−1) or the AT2 receptor antagonist PD 123319 (30 mg kg−1 d−1). Treatment was started 7 days prior to surgery. On day 1, 3, 7 and 14 after MI, gene expression and protein levels of calpain I, II and calpastatin were determined in left ventricular free wall (LVFW) and interventricular septum (IS). At day 3 and 14 post MI, morphological investigations were performed.
Calpain I mRNA expression and protein levels were increased in IS 14 days post MI, whereas mRNA expression and protein levels of calpain II were maximally increased in LVFW 3 days post MI. Ramipril and valsartan decreased mRNA and protein up‐regulation of calpain I and II, and reduced infarct size and interstitial fibrosis. PD 123319 did not affect calpain I or II up‐regulation in the infarcted myocardium, but decreased interstitial fibrosis. Calpastatin expression and translation were not affected by AT receptor antagonists or ACE inhibitor.
Our data demonstrate a distinct, temporary‐spatial up‐regulation of calpain I and II following MI confer with the hypothesis of calpain I being involved in cardiac remodelling in the late and calpain II contributing to cardiac tissue damage in the early phase of MI. The up‐regulation of calpain I and II is partly mediated via the AT1 receptor and can be reduced by ACE inhibitors and AT1 receptor antagonists.
Recent studies demonstrated that the cardiac calpain system is activated during ischaemic events and is involved in cardiomyocyte injury. The aim of this study was to investigate the contribution of AT1 and AT2 receptors in the regulation of calpain‐mediated myocardial damage following myocardial infarction (MI).
Infarcted animals were treated either with placebo, the ACE inhibitor ramipril (1 mg kg−1 d−1), the AT1 receptor antagonist valsartan (10 mg kg−1 d−1) or the AT2 receptor antagonist PD 123319 (30 mg kg−1 d−1). Treatment was started 7 days prior to surgery. On day 1, 3, 7 and 14 after MI, gene expression and protein levels of calpain I, II and calpastatin were determined in left ventricular free wall (LVFW) and interventricular septum (IS). At day 3 and 14 post MI, morphological investigations were performed.
Calpain I mRNA expression and protein levels were increased in IS 14 days post MI, whereas mRNA expression and protein levels of calpain II were maximally increased in LVFW 3 days post MI. Ramipril and valsartan decreased mRNA and protein up‐regulation of calpain I and II, and reduced infarct size and interstitial fibrosis. PD 123319 did not affect calpain I or II up‐regulation in the infarcted myocardium, but decreased interstitial fibrosis. Calpastatin expression and translation were not affected by AT receptor antagonists or ACE inhibitor.
Our data demonstrate a distinct, temporary‐spatial up‐regulation of calpain I and II following MI confer with the hypothesis of calpain I being involved in cardiac remodelling in the late and calpain II contributing to cardiac tissue damage in the early phase of MI. The up‐regulation of calpain I and II is partly mediated via the AT1 receptor and can be reduced by ACE inhibitors and AT1 receptor antagonists.
British Journal of Pharmacology (2001) 132, 767–777; doi:10.1038/sj.bjp.0703860
DOI: 10.1038/sj.bjp.0703860
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