Chronic endothelin A receptor blockade in lambs with increased pulmonary blood flow and pressure.

Fratz, S; Meyrick, B; Ovadia, B; Johengen, MJ; Reinhartz, O; Azakie, A; Ross, G; Fitzgerald, R; Oishi, P; Hess, J; Black, SM; Fineman, JR

doi:10.1152/ajplung.00093.2004

2004

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Titel:: Chronic endothelin A receptor blockade in lambs with increased pulmonary blood flow and pressure.
Dokumenttyp:: Journal Article
Autor(en):: Fratz, S; Meyrick, B; Ovadia, B; Johengen, MJ; Reinhartz, O; Azakie, A; Ross, G; Fitzgerald, R; Oishi, P; Hess, J; Black, SM; Fineman, JR
Abstract:: Endothelin receptor blockade is an emerging therapy for pulmonary hypertension. However, hemodynamic and structural effects and potential changes in endogenous nitric oxide (NO)-cGMP and endothelin-1 signaling of chronic endothelin A receptor blockade in pulmonary hypertension secondary to congenital heart disease are unknown. Therefore, the objectives of this study were to determine hemodynamic and structural effects and potential changes in endogenous NO-cGMP and endothelin-1 signaling of chronic endothelin A receptor blockade in a lamb model of increased pulmonary blood flow following in utero placement of an aortopulmonary shunt. Immediately after spontaneous birth, shunt lambs were treated lifelong with either an endothelin A receptor antagonist (PD-156707) or placebo. At 4 wk of age, PD-156707-treated shunt lambs (n = 6) had lower pulmonary vascular resistance and right atrial pressure than placebo-treated shunt lambs (n = 8, P < 0.05). Smooth muscle thickness or arterial number per unit area was not different between the two groups. However, the number of alveolar profiles per unit area was increased in the PD-156707-treated shunt lambs (190.7 +/- 5.6 vs. 132.9 +/- 10.0, P < 0.05). Plasma endothelin-1 and cGMP levels and lung NOS activity, cGMP, eNOS, preproendothelin-1, endothelin-converting enzyme-1, endothelin A, and endothelin B receptor protein levels were similar in both groups. We conclude that chronic endothelin A receptor blockade attenuates the progression of pulmonary hypertension and augments alveolar growth in lambs with increased pulmonary blood flow.
Zeitschriftentitel:: Am J Physiol Lung Cell Mol Physiol
Jahr:: 2004
Band / Volume:: 287
Heft / Issue:: 3
Seitenangaben Beitrag:: L592-7
Sprache:: eng
Volltext / DOI:: doi:10.1152/ajplung.00093.2004
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/15155268
Print-ISSN:: 1040-0605
TUM Einrichtung:: Klinik für Kinderkardiologie und angeborene Herzfehler (Prof. Hess)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Lehr- und Forschungskooperationen mit den Kliniken und Instituten am Deutschen Herzzentrum Klinik für Kinderkardiologie und angeborene Herzfehler (DHM) (Prof. Ewert)2004