Open AccessBosentan Effects in Hypoxic Pulmonary Vasoconstriction: Preliminary Study in Subjects with or without High Altitude Pulmonary Edema‐History
Author(s) -
Pham Isabelle,
Wuerzner Grégoire,
Richalet JeanPaul,
Peyrard Séverine,
Azizi Michel
Publication year - 2012
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.4103/2045-8932.94824
Subject(s) - bosentan , medicine , hypoxic pulmonary vasoconstriction , high altitude pulmonary edema , hypoxia (environmental) , pulmonary hypertension , placebo , cardiology , pulmonary artery , vasoconstriction , peripheral edema , endothelin receptor , endothelin receptor antagonist , pulmonary edema , endothelin 1 , anesthesia , lung , adverse effect , pathology , receptor , oxygen , chemistry , alternative medicine , organic chemistry
Hypoxia‐induced pulmonary vasoconstriction in patients with a medical history of high‐altitude pulmonary edema (HAPE) may involve activation of the endothelin‐1 (ET‐1) pathway. We, therefore, compared the effect of the ETA/ETB receptor antagonist, bosentan, on pulmonary artery systolic pressure (PASP) in healthy subjects with (HS: HAPE subjects, n =5) or without a HAPE‐history (CS: Control subjects, n =10). A double‐blind, placebo‐controlled, randomized, crossover design was performed in order to study the effects on PASP of a single oral dose of bosentan (250 mg) after 90 min exposure to normobaric hypoxia (FiO 2 =0.12). In normoxia, PASP, evaluated by echocardiography, was 23.4±2.7 mmHg in CS and 28±5.8 mmHg in HS (NS). During the placebo period, hypoxia induced a significant decrease in SaO 2 , PaO 2 and PCO 2 and increase in pH in both CS and HS. Pulmonary arterial systolic pressure was also significantly increased (+8.5±5.0 mmHg in CS; +13.4±3.1 mmHg in HS) and reached significantly higher levels in HS than in CS (P=0.02). Bosentan significantly but similarly blunted the hypoxia‐induced increase in PASP in both CS (Bosentan: 27.0±3.3 mmHg; placebo: 32.1±3.5 mmHg; P<0.01) and HS (Bosentan: 35.0±2.9 mmHg; placebo: 41.4±7.6 mmHg; P<0.05), (CS 5.2±5.3 vs. HS −6.4±5.2 mmHg, NS). Bosentan did not have a major effect on the hypoxia‐induced changes in blood gas, or on cardiac output (CO) and systemic blood pressure (SBP), which were not modified by hypoxia. Plasma ET‐1 in hypoxia during the bosentan period was 2.8 times higher than during for both CS and HS. A single oral dose of bosentan similarly blunted the hypoxia‐induced increase in PASP both in healthy and HAPE‐susceptible subjects, without altering CO or SBP.