Effect of temporary tracheal occlusion on the endothelin system in experimental cases of diaphragmatic hernia.
Previously, the authors have shown that tracheal occlusion (TO) partially reverses the onset of congenital diaphragmatic hernia (CDH)-induced pulmonary hypertension (PH) and abnormal pulmonary vascular development whereas release of the occlusion (TR) abolishes these clinical benefits. As a consequence of their mitogenic and vasoactive properties, the authors hypothesize that the expression of endothelin (ET)-1 and ET receptor (ETA) genes is increased in lungs of CDH lambs, and that this increase is abolished partially in CDH + TO but not in CDH + TO + TR. A surgical left-sided CDH was created in fetal lambs at 80 days of gestation (gd), followed by TO at 108 gd, and by TR at 129 gd. Four groups were compared: CDH, CDH + TO, CDH + TO + TR, and nonoperated controls (C). Assessment of mRNA expression by Northern blot showed significantly lower ET-1 and ETA levels in the CDH group than in the CDH + TO +/- TR groups (P < .05). Endothelin protein expression levels were lower in CDH +/- TO +/- TR groups when compared with controls for airways and vessels (P < .05) with the exception of endothelial cells. In contrast, ETA protein expression levels were higher in CDH +/- TO +/- TR groups compared with controls for airways and blood vessels smooth muscles (P < .05). These results suggest that involvement of the endothelin system in the pulmonary hypertension associated with CDH is limited. However, the endothelin system appears to be modulated during development.
Cloutier
Marc
M
Pediatrics, Centre Hospitalier Universitaire de Québec, Laval University, Sainte-Foy, Québec, Canada.
Seaborn
Tommy
T
Piedboeuf
Bruno
B
Bratu
Ioana
I
Flageole
Hélène
H
Laberge
Jean-Martin
JM
D000818:Animals; D021721:Balloon Occlusion / Q000009:adverse effects* / Q000379:methods; D015152:Blotting, Northern; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics; D005315:Fetal Diseases / Q000503:physiopathology / Q000628:therapy*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006548:Hernia, Diaphragmatic / Q000150:complications / Q000378:metabolism; D065630:Hernias, Diaphragmatic, Congenital; D007124:Immunoenzyme Techniques; D008168:Lung / Q000002:abnormalities / Q000098:blood supply / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000096:biosynthesis / Q000235:genetics; D012756:Sheep; D014132:Trachea
D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A