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Acta Physiologica Congress

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Acta Physiologica 2011; Volume 201, Supplement 682
The 90th Annual Meeting of The German Physiological Society
3/26/2011-3/29/2011
Regensburg, Germany


CATECHOLAMINE INFUSION INDUCES EXTRACELLULAR REMODELING IN THE RAT LUNG
Abstract number: P187

*Rassler1 B., Marx1 G., Zimmer1 H.-G.

In previous studies with continuous catecholamine (CA) infusion in rats, we observed the development of pulmonary injury which resembled acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) in humans. It was characterized by edema, inflammation and histologic signs of fibrotic changes. The objective of the present study was to examine whether remodeling of the extracellular matrix (ECM) in the lung of Sprague-Dawley rats occurs after 8–72h of infusion of either norepinephrine (NE, n = 23) or selective a- (phenylephrine, PE, n = 18) or b-adrenergic (isoproterenol, ISO, n = 17) agonists. Rats infused with 0.9% NaCl solution served as controls (C, n = 22). We investigated mRNA expression of ECM molecules such as collagen type I (Coll1) and III (Coll3), colligin, matrix metalloproteinase (MMP)-2 and its specific tissue inhibitor (TIMP-2) as well as transforming growth factor (TGF)-b isoforms in lung tissue. After 72h of infusion with either type of CAs, mRNA expression of Coll1 was significantly elevated, and this effect was most pronounced with NE (5.5-fold of C, p < 0.001). Likewise, expression of colligin increased significantly (1.6-fold of C, p = 0.004) while Coll3 did not significantly increase (p = 0.09). Enhanced collagen expression was accompanied by a significant increase in mRNA expression of MMP-2 and TIMP-2 (p < 0.001). PE and ISO induced similar but less pronounced responses. This indicates that mRNA expression of these ECM components is stimulated via a- and b-adrenoceptors. Moreover, activity of MMP-2 protein was significantly elevated after 72h of NE, but not after PE or ISO infusion, respectively. TGF-b isoforms were also elevated after 72h of infusion. This effect was stronger with PE than with ISO or NE indicating that stimulation of TGF-b mRNA expression is mainly an a-adrenergic effect. Cardiac hypertrophy, on the other hand, was most pronounced after ISO infusion and is therefore considered to be a direct inotropic effect rather than a consequence of pulmonary congestion and fibrosis.

To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 201, Supplement 682 :P187

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