| Endothelin receptors blockade blunts hypoxia-induced increase in PAP in humans. | |
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MedLine Citation:
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PMID: 20415698 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Activation of the endothelin-1 (ET-1) pathway may be involved in hypoxia-induced pulmonary vasoconstriction, increase in pulmonary pressure and high altitude pulmonary oedema. Thus, we investigated the effect of the ETA/ETB receptor antagonist, bosentan, on pulmonary artery systolic pressure (PASP) in healthy subjects (n = 10). DESIGN: We used a double-blind, placebo-controlled, randomized, cross-over design to study the effects of a single oral dose of bosentan (250 mg) on PASP after 90-min-exposure to normobaric hypoxia (FiO(2) = 0.12). We measured PASP and cardiac output by echocardiography, systolic arterial blood pressure, arterial O(2) saturation (SaO(2)), and blood gases at rest and during a sub-maximal exercise. RESULTS: PASP in normoxia at rest was 23.5 +/- 2.7 and during exercise 39.8 +/- 11.6 mmHg (P < 0.0001). During the placebo period, hypoxia induced a significant decrease in SaO(2), PaO(2) and PCO(2) and increase in pH. PASP at rest increased significantly: 32.1 +/- 3.5 mmHg (P < 0.001 vs. normoxia). Bosentan significantly blunted the hypoxia-induced increase in PASP: bosentan: 27.0 +/- 3.3 mmHg, P = 0.002 vs. placebo at rest, but not during exercise: bosentan 39.8 +/- 11.6 vs. placebo 43.0 +/- 8.5 mmHg, ns. Bosentan had no effect on the hypoxia-induced changes in blood gases, or on cardiac output and systolic arterial blood pressure, which were not modified by hypoxia. CONCLUSION: A single oral dose of bosentan blunted an acute hypoxia-induced increase in PASP in healthy subjects, without altering cardiac output or systemic blood pressure. |
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Authors:
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I Pham; G Wuerzner; J-P Richalet; S Peyrard; M Azizi |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of clinical investigation Volume: 40 ISSN: 1365-2362 ISO Abbreviation: Eur. J. Clin. Invest. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-04-26 Completed Date: 2010-06-29 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0245331 Medline TA: Eur J Clin Invest Country: England |
Other Details:
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Languages: eng Pagination: 195-202 Citation Subset: IM |
Affiliation:
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Universit? Paris 13-UFR SMBH, EA 2363, Bobigny, France. isabelle.pham@jvr.aphp.fr |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00026081 |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Adult Anoxia / drug therapy*, physiopathology Antihypertensive Agents / administration & dosage, pharmacology* Blood Gas Analysis Blood Pressure / drug effects* Cardiac Output / drug effects Cross-Over Studies Double-Blind Method Echocardiography Exercise / physiology Humans Male Middle Aged Oxygen / metabolism Pulmonary Artery / drug effects Pulmonary Circulation / drug effects* Receptors, Endothelin / antagonists & inhibitors* Sulfonamides / administration & dosage, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Receptors, Endothelin; 0/Sulfonamides; 147536-97-8/bosentan; 7782-44-7/Oxygen |
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