Transcriptional and translational regulation of calpain in the rat heart after myocardial infarction - effects of AT(1) and AT(2) receptor antagonists and ACE inhibitor

1 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 AT(1) and AT(2) receptor s in the regulation of calpain-mediated myocardial damage following myocard ial infarction (MI). 2 Infarcted animals were treated either with placebo, the ACE inhibitor ram ipril (1 mg kg(-1) d(-1)), the AT(1) receptor antagonist valsartan (10 mg k g(-1) d(-1)) or the AT(2) 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 aft er MI, gene expression and protein levels of calpain I, II and calpastatin were determined in left ventricular free wall (LVFW) and interventricular s eptum (IS). At day 3 and 14 post MI, morphological investigations were perf ormed. 3 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 max imally increased in LVFW 3 days post MI. Ramipril and valsartan decreased m RNA 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-reg ulation in the infarcted myocardium, but decreased interstitial fibrosis. C alpastatin expression and translation were not affected by AT receptor anta gonists or ACE inhibitor. 4 Our data demonstrate a distinct, temporary-spatial up-regulation of calpa in I and II following MI confer with the hypothesis of calpain I being invo lved in cardiac remodelling in the late and calpain II contributing to card iac tissue damage in the early phase of MI. The up-regulation of calpain I and II is partly mediated via the AT(1) receptor and can be reduced by ACE inhibitors and AT(1) receptor antagonists.