title: Endothelin-1- and endothelin-receptors in lung biopsies of patients with pulmonary hypertension due to congenital heart disease.
abstract: Endothelin-1 (ET-1), with its vasoconstrictive and proliferation-stimulating effects, could play a role in the pathogenesis of primary pulmonary hypertension. We investigated the relationship between the ET-1 like immunoreactivity and the ET-receptor density, the grade of the pulmonary vasculopathy, and properties of the pulmonary circulation in patients with pulmonary hypertension due to congenital heart disease. Twenty-six patients with a median age of 1 year and 1 month (6 weeks - 17 years - 9 months) were assigned to group I (n = 15) with a pulmonary to systemic flow ratio (Qp/Qs) > or = 1.5 and a pulmonary to systemic resistance ratio (Rp/Rs) < or = 0.3 ("high flow - low resistance group") and to group II (n = 11) with a Qp/Qs < 1.5 and an Rp/Rs > 0.3 ("low flow - high resistance group"). Patients belonging to group II showed a higher ET(A)-receptor density in lung arteries (p < 0.05) and parenchyma (p < 0.01) than patients in group I. Patients with the highest ET-1 like immunoreactivity in lung artery walls also showed a trend towards a higher ET(A)-receptor density. The ET(B)-receptor expression was low and not related to any of the above factors. Our results suggest that the paracrine lung ET-1 system is up-regulated in pediatric patients with secondary pulmonary hypertension associated with congenital heart disease.
authors.affiliation: Department of Pediatric Pathology and Placentology, Universitätsklinikum Charité, Campus-Virchow-Klinikum, Humboldt Universität zu Berlin, Germany. jens.lutz@uni-essen.de
authors.forename: J
authors.initials: J
authors.lastname: Lutz
authors.forename: M
authors.initials: M
authors.lastname: Gorenflo
authors.forename: M
authors.initials: M
authors.lastname: Habighorst
authors.forename: M
authors.initials: M
authors.lastname: Vogel
authors.forename: P E
authors.initials: PE
authors.lastname: Lange
authors.forename: B
authors.initials: B
authors.lastname: Hocher
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019332:Endothelin-1 / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism*; D007150:Immunohistochemistry; D007223:Infant; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D017466:Receptors, Endothelin / Q000032:analysis / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D017466:Receptors, Endothelin