AJP - Lung Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 287: L592-L597, 2004. First published May 21, 2004; doi:10.1152/ajplung.00093.2004
1040-0605/04 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/3/L592    most recent
00093.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fratz, S.
Right arrow Articles by Fineman, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fratz, S.
Right arrow Articles by Fineman, J. R.

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

Sohrab Fratz,1,2 Barbara Meyrick,3 Boaz Ovadia,2 Michael J. Johengen,2 Olaf Reinhartz,2 Anthony Azakie,2 Greg Ross,2 Robert Fitzgerald,2 Peter Oishi,2 John Hess,1 Stephen M. Black,4 and Jeffrey R. Fineman2

1Department of Pediatric Cardiology and Congenital Heart Disease, Deutsches Herzzentrum München, 80636 Munich, Germany; 2Department of Pediatrics and the Cardiovascular Research Institute, University of California, San Francisco, California 94143; 3Departments of Pathology and Medicine, Vanderbilt University, Nashville, Tennessee 37235; and 4Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana 59812

Submitted 15 March 2004 ; accepted in final form 17 May 2004

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.

pulmonary heart disease; congenital heart defect


Address for reprint requests and other correspondence: S. Fratz, Dept. of Pediatric Cardiology and Congenital Heart Disease, Deutsches Herzzentrum München, Klinik an der Technischen Universität München, Lazarettstr. 36, 80636 Munich, Germany (E-mail: fratz{at}dhm.mhn.de)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.