Original articleModulating effect of a selective endothelin A receptor antagonist on pulmonary endothelin system protein expression in experimental diaphragmatic hernia
Section snippets
Material and methods
Pathogen-free pregnant crossbred ewes were obtained from Thomas Morris Inc (Reisterstown, Md). The current protocol has been carried out in accordance with the guidelines of the Canadian Council of Animal Care and was authorized by the local Animal Care and Use Committee at Laval University (no. 98-150).
Overall immunostaining distribution of ETs, ETA, and ETB protein expression within lung subcompartments of all 4 lamb groups
In all 4 groups of lambs, protein expression of ETs was more intense in the airway subcompartments than in the pulmonary vasculature or within the parenchyma. The airway epithelium subcompartment presented the most intense staining, whereas the weakest signal was observed in the pulmonary vascular endothelium. Although of less intensity (ETs > ETA > ETB), the expression of ETA and ETB pulmonary proteins did reveal similar distribution patterns to that observed for ET-related peptides. The
Discussion
In the present study, after a short period of ventilation, we did not observe any significant difference in the expression levels of ETs, ETA, and ETB proteins in the left or right lungs of any experimental left-sided CDH newborn lambs when compared with controls. However, treatment of intact newborn lambs with a potent nonpeptidic and selective ETA antagonist, atrasentan, is associated with a significant increase in ETA protein expression level in the vascular adventitia and airway epithelium.
Acknowledgments
This study was supported by a grant 48086 from the Canadian Institutes of Health Research/University Industry (Abbott Laboratories Inc, Abbott Park, IL) and the Fondation de la Recherche sur les Maladies Infantiles, Montreal, Quebec, Canada. This study was also supported by an FRSQ and university/industry research scholarship (BB), and an Fonds de recherche en santé du Québec/Fonds pour la formation de chercheurs et l'aide à la recherche PhD studentship (MK). We thank Paul Khan for his help in
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