RT Journal Article
SR Electronic
T1 Endothelin receptor expression in idiopathic pulmonary arterial hypertension: effect of bosentan and epoprostenol treatment
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 851
OP 860
DO 10.1183/09031936.00167010
VO 38
IS 4
A1 S.M. Hall
A1 N. Davie
A1 N. Klein
A1 S.G. Haworth
YR 2011
UL http://erj.ersjournals.com/content/38/4/851.abstract
AB Endothelin receptor antagonists are used to treat idiopathic pulmonary arterial hypertension (IPAH), but human pulmonary arterial endothelin receptor expression is not well defined. We hypothesised that disease and treatment would modify normal receptor distribution in pulmonary resistance arteries of children. Using immunohistochemistry and semiquantitative analysis, we investigated endothelin receptor subtypes A and B (ETA and ETB, respectively), and endothelial nitric oxide synthase (eNOS) expression in peripheral pulmonary arteries of tissue from untreated children with IPAH (n=7), following extended combined bosentan and epoprostenol therapy (n=5) and from normal subjects (n=5). Clinical, haemodynamic and pathological abnormalities were severe and advanced in all IPAH cases. ETA was detected in pulmonary arterial endothelial cells of all normal and diseased tissue and cultured cells. Endothelial ETA, ETB and eNOS expression was reduced in patent, plexiform and dilatation lesions of untreated cases, but in treated cases, ETA and ETB were normal and eNOS increased. In smooth muscle, ETA expression was reduced in treated cases but ETB expression increased in all arteries of both treated and untreated cases. In summary, ETA is expressed on human pulmonary arterial endothelium. In IPAH, combination treatment with bosentan and epoprostenol had a more marked influence on endothelin receptor expression of endothelial than smooth muscle cells.