Document Detail

Endothelin receptors blockade blunts hypoxia-induced increase in PAP in humans.
MedLine Citation:
PMID:  20415698     Owner:  NLM     Status:  MEDLINE    
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.
I Pham; G Wuerzner; J-P Richalet; S Peyrard; M Azizi
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of clinical investigation     Volume:  40     ISSN:  1365-2362     ISO Abbreviation:  Eur. J. Clin. Invest.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-04-26     Completed Date:  2010-06-29     Revised Date:  2013-06-18    
Medline Journal Info:
Nlm Unique ID:  0245331     Medline TA:  Eur J Clin Invest     Country:  England    
Other Details:
Languages:  eng     Pagination:  195-202     Citation Subset:  IM    
Université Paris 13-UFR SMBH, EA 2363, Bobigny, France.
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MeSH Terms
Administration, Oral
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
Exercise / physiology
Middle Aged
Oxygen / metabolism
Pulmonary Artery / drug effects
Pulmonary Circulation / drug effects*
Receptors, Endothelin / antagonists & inhibitors*
Sulfonamides / administration & dosage,  pharmacology*
Reg. No./Substance:
0/Antihypertensive Agents; 0/Receptors, Endothelin; 0/Sulfonamides; 7782-44-7/Oxygen; Q326023R30/bosentan

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