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Acta Physiologica 2006; Volume 186, Supplement 650
Joint Meeting of The German Society of Physiology and The Federation of European Physiological Societies 2006
3/26/2006-3/29/2006
Ludwig-Maximilians-University, Munich
NOREPINEPHRINE-INDUCED ECM TURNOVER AND EARLY REMODELLING OF THE MOUSE HEART
Abstract number: OM09-54
Meier1 H, Bullinger1 J, Deten1 A, Zimmer1 HG, Briest1 W
1Carl-Ludwig-Institut fr Physiologie
Matrix metalloproteinases (MMPs) play an important role in myocardial remodelling, and MMP activity can be regulated by the tissue inhibitors of the metalloproteinases (TIMPs). Norepinephrine (NE)-induced hypertrophy of the left ventricle (LV) in the rat is associated with remodelling of the extracellular matrix (ECM). In the present study it was analyzed, whether functional and molecular parameters are altered by NE also the heart of mice and which role TIMPs may play. NE was administered sc in balb/c mice with different concentrations (0.13, 0.25, 0.38 mg/kg per h) for 3 days and for 4 h, 1 and 3 days with 0.25 mg/kg per h NE. The mRNA of natriuretic peptides (NPs), of MMPs, of TIMPs as well as of collagen I and III was detected by ribonuclease protection assay. The activity of MMP-2 was measured. NE induced concentration-dependently LV hypertrophy, detected by increased LV weight/body weight (LVW/BW) ratio and increased mRNA expression of ANP. NE led to latent insufficiency of the LV as evidenced by the dose-dependent attenuation of the elevated LVSP and contractility and by histological signs of congestion in the lung. During NE-induced evolving LV hypertrophy, induction of collagen type I and type III expression was accompanied by concentration and time dependent elevation of TIMP 1 expression. This occurred predominantly in myocytes and correlated with increased collagen.
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Acta Physiologica 2006; Volume 186, Supplement 650 :OM09-54