Endothelin receptors blockade blunts hypoxia-induced increase in PAP in humans
Eur J Clin Invest 2010; 40 (3): 195–202 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, bos...
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Published in | European journal of clinical investigation Vol. 40; no. 3; pp. 195 - 202 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.03.2010
Wiley-Blackwell |
Subjects | |
Online Access | Get full text |
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Summary: | Eur J Clin Invest 2010; 40 (3): 195–202
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 (FiO2 = 0·12). We measured PASP and cardiac output by echocardiography, systolic arterial blood pressure, arterial O2 saturation (SaO2), 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 SaO2, PaO2 and PCO2 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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Bibliography: | istex:4748ACA5C81EA87F420BF1DA304DC11AB3844798 ArticleID:ECI2254 ark:/67375/WNG-6WJ2PRMF-8 Clinical trial registration information NCT0026081. http://www.clinicaltrials.gov Randomized clinical trial ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-News-1 ObjectType-Feature-3 content type line 23 |
ISSN: | 0014-2972 1365-2362 |
DOI: | 10.1111/j.1365-2362.2010.02254.x |