![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
RC Lindenschmidt and HP Witschi
Current concepts of collagen metabolism suggest that fibroblasts tightly control collagen production. One of the possible mechanisms of control is via the cyclic nucleotides, cyclic AMP (cAMP) and cyclic GMP (cGMP). Beta adrenergic agonists, by elevating intracellular cAMP levels, have been shown in vitro to suppress fibroblast collagen production; whereas beta adrenergic antagonists were effective in removing this suppression by blocking the rise in cAMP. In the present study with mice, we showed that administration of the beta adrenergic antagonist, propranolol, at a dose demonstrated to decrease the ratio of cAMP to cGMP, resulted in an elevation in total lung collagen in vivo. The increase in collagen was evident only when propranolol was administered before and during acute lung damage induced by either butylated hydroxytoluene, bleomycin or high concentrations of oxygen. There was no increase in lung collagen when propranolol administration was delayed after injury or when given to an undamaged lung. We propose that via beta adrenergic blockade by propranolol, fibroblasts involved in the normal reparative process may have lost a mechanism for regulatory control, resulting in excessive deposition of collagen.
This article has been cited by other articles:
|
|
 |
|
  X. Liu, S. Q. Sun, and R. S. Ostrom Fibrotic Lung Fibroblasts Show Blunted Inhibition by cAMP Due to Deficient cAMP Response Element-Binding Protein Phosphorylation J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 678 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Baouz, J. Giron-Michel, B. Azzarone, M. Giuliani, F. Cagnoni, S. Olsson, R. Testi, G. Gabbiani, and G. W. Canonica Lung myofibroblasts as targets of salmeterol and fluticasone propionate: inhibition of {alpha}-SMA and NF-{kappa}B Int. Immunol., November 1, 2005; 17(11): 1473 - 1481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Liu, R. S. Ostrom, and P. A. Insel cAMP-elevating agents and adenylyl cyclase overexpression promote an antifibrotic phenotype in pulmonary fibroblasts Am J Physiol Cell Physiol, May 1, 2004; 286(5): C1089 - C1099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Card, W. J. Racz, J. F. Brien, S. B. Margolin, and T. E. Massey Differential Effects of Pirfenidone on Acute Pulmonary Injury and Ensuing Fibrosis in the Hamster Model of Amiodarone-Induced Pulmonary Toxicity Toxicol. Sci., September 1, 2003; 75(1): 169 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Ostrom, J. E. Naugle, M. Hase, C. Gregorian, J. S. Swaney, P. A. Insel, L. L. Brunton, and J. G. Meszaros Angiotensin II Enhances Adenylyl Cyclase Signaling via Ca2+/Calmodulin: Gq-Gs CROSS-TALK REGULATES COLLAGEN PRODUCTION IN CARDIAC FIBROBLASTS J. Biol. Chem., June 27, 2003; 278(27): 24461 - 24468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Card, W. J. Racz, J. F. Brien, and T. E. Massey Attenuation of Amiodarone-Induced Pulmonary Fibrosis by Vitamin E Is Associated with Suppression of Transforming Growth Factor-beta 1 Gene Expression but Not Prevention of Mitochondrial Dysfunction J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 277 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. H. Chung, B. M. Bennett, W. J. Racz, J. F. Brien, and T. E. Massey Induction of c-jun and TGF-beta 1 in Fischer 344 rats during amiodarone-induced pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1180 - L1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shores, K. R. Berger, E. A. Murphy, and R. E. Pyeritz Progression of Aortic Dilatation and the Benefit of Long-Term {beta}-Adrenergic Blockade in Marfan's Syndrome N. Engl. J. Med., May 12, 1994; 330(19): 1335 - 1341. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
