Original ArticleDownregulation of the Endothelin System of Lung Myofibroblasts in Congestive Heart FailurePréfontaine, Annick MSc*; Calderone, Angelino PhD*†; Dupuis, Jocelyn MD, PhD*‡Author Information From the *Research Center, Montreal Heart Institute; †Department of Physiology; and ‡Department of Medicine, Université de Montréal, Montreal, Quebec, Canada. Received for publication January 22, 2009; accepted May 7, 2009. Supported by the Canadian Institutes of Health Research, Fonds de la recherche en santé du Québec, and the Fondation de l'Institut de Cardiologie de Montréal. The authors report no conflicts of interest. Reprints: Jocelyn Dupuis, MD, PhD, Research Center, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, Canada H1T 1C8 (e-mail: [email protected]). Journal of Cardiovascular Pharmacology: August 2009 - Volume 54 - Issue 2 - p 147-153 doi: 10.1097/FJC.0b013e3181ad7d57 Buy Metrics Abstract Congestive heart failure (CHF) causes lung remodelling with thickening of the alveolar septa and proliferation of myofibroblasts (MYF). Endothelin-1 (ET-1) is increased in CHF and may contribute to this process. CHF was induced in rats by myocardial infarction. After three weeks there was lung remodelling with thickening of alveolar septa and increases in 5′-bromodeoxyuridine uptake and vimentin expression (P < 0.05). The mitogenic and protein synthesis response of MYF to ET-1 (10 nM) were assessed by 3H-thymidine and 3H-leucine incorporation respectively. The mitogenic response in CHF (19.0 ± 3.0%, mean ± SEM) was less than for sham rats (35 ± 5.4%, P < 0.05). This was associated with a lower production of ET-1 by CHF MYF (15.15 ± 5.67 fmol/ml) compared to sham (33.66 ± 13.22 fmol/ml; P < 0.05). Additionally, protein expression of ETA (0.36 ± 0.038 AU) and ETB receptors (0.24 ± 0.075 AU) were reduced in CHF compared to shams (0.65 ± 0.086 AU and 0.81 ± 0.21 AU respectively; P < 0.05). There is a downregulation of the ET system of lung MYF in CHF with reduced proliferation in response to ET-1. This may represent a protective adaptation to counteract lung remodelling in response to chronic exposure to high levels of ET-1. © 2009 Lippincott Williams & Wilkins, Inc.