title: Catecholamines can induce pulmonary remodeling in rats.
abstract: OBJECTIVE
  Previously, we found that catecholamine (CA) infusion in rats induced pulmonary injury with edema and inflammation resembling acute lung injury in humans. Here, we examined effects of norepinephrine (NE) and of selective α- and β-adrenergic agonists on the remodeling of pulmonary extracellular matrix.
  
  
  METHODS
  Eighty rats were infused over 8-72 h with NE, phenylephrine (PE), isoproterenol (ISO) or NaCl solution. We investigated mRNA expression of collagen, matrix metalloproteinase (MMP)-2, its tissue inhibitor (TIMP-2) and transforming growth factor (TGF)-β isoforms in lung tissue. Additionally, lung histology, hemodynamic function and cardiac hypertrophy were evaluated.
  
  
  RESULTS
  After 72 h of infusion, lung histology showed beginning fibrosis and vascular hypertrophy. Collagen type I, MMP-2 and TIMP-2 mRNA expression were significantly elevated. All these effects were most pronounced with NE while PE and ISO induced weaker responses. TGF-β mRNA expression was also elevated after 72 h, predominantly after PE infusion. Cardiac hypertrophy was most pronounced after ISO infusion.
  
  
  CONCLUSIONS
  CA infusion over 72 h may induce pulmonary remodeling. Mainly α-adrenergic but also β-adrenergic mechanisms contribute to these processes. In contrast, cardiac hypertrophy is predominantly mediated by β-adrenergic stimulation and hence, is considered to be a direct adrenergic effect rather than a consequence of pulmonary fibrosis.
authors.affiliation: Carl-Ludwig-Institute of Physiology, University of Leipzig, Leipzig, Germany. Beate.Rassler@medizin.uni-leipzig.de
authors.forename: Beate
authors.initials: B
authors.lastname: Rassler
authors.forename: Grit
authors.initials: G
authors.lastname: Marx
authors.forename: Katrin
authors.initials: K
authors.lastname: Schierle
authors.forename: Heinz-Gerd
authors.initials: HG
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; D010656:Phenylephrine; D020778:Matrix Metalloproteinase 2; D007545:Isoproterenol; D009638:Norepinephrine