Abstract | BACKGROUND: METHODS AND RESULTS: Thirty 3-week-old piglets were randomized to placebo or to bosentan 15 mg/kg BID after the anastomosis of the left subclavian artery to the pulmonary arterial trunk or after a sham operation. Three months later, the animals underwent a hemodynamic evaluation followed by cardiac and pulmonary tissue sampling for morphometry, immunohistochemistry, and real-time quantitative PCR. Chronic systemic-to-pulmonary shunting increased circulating plasma ET-1, pulmonary mRNA for ET-1, ET(B) receptor, inducible NO synthase, VEGF, and pulmonary ET-1 and VEGF proteins. There were increases in myocardial mRNA for ET(A) receptor and VEGF and in myocardial VEGF protein. Pulmonary and myocardial tissue mRNA for tenascin did not change. Normalized-flow pulmonary artery pressure increased from 20 (2) to 33 (1) mm Hg [mean (SEM)], arteriolar medial thickness increased on average by 83%, and these changes were completely prevented by bosentan therapy. Right ventricular end-systolic elastance increased in proportion to pulmonary arterial elastance with or without bosentan. CONCLUSIONS:
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Authors | Benoît Rondelet, François Kerbaul, Sophie Motte, Ronald van Beneden, Myriam Remmelink, Serge Brimioulle, Kathleen McEntee, Pierre Wauthy, Isabelle Salmon, Jean-Marie Ketelslegers, Robert Naeije |
Journal | Circulation
(Circulation)
Vol. 107
Issue 9
Pg. 1329-35
(Mar 11 2003)
ISSN: 1524-4539 [Electronic] United States |
PMID | 12628956
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antihypertensive Agents
- Endothelial Growth Factors
- Endothelin Receptor Antagonists
- Endothelin-1
- Endothelins
- Intercellular Signaling Peptides and Proteins
- Lymphokines
- RNA, Messenger
- Sulfonamides
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- Nitric Oxide
- Bosentan
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Topics |
- Animals
- Antihypertensive Agents
(therapeutic use)
- Bosentan
- Endothelial Growth Factors
(biosynthesis, genetics)
- Endothelin Receptor Antagonists
- Endothelin-1
(biosynthesis, genetics)
- Endothelins
(physiology)
- Hemodynamics
- Hypertension, Pulmonary
(etiology, metabolism, prevention & control)
- Intercellular Signaling Peptides and Proteins
(biosynthesis, genetics)
- Lung
(metabolism)
- Lymphokines
(biosynthesis, genetics)
- Myocardium
(metabolism)
- Nitric Oxide
(biosynthesis, genetics)
- Pulmonary Artery
(pathology, surgery)
- Pulmonary Circulation
- RNA, Messenger
(biosynthesis)
- Sulfonamides
(therapeutic use)
- Swine
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
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