Role of Endothelin-1 in Exposure to High Altitude : Acute Mountain Sickness and Endothelin-1 (ACME-1) Study
: Acute Mountain Sickness and Endothelin-1 (ACME-1) Study
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Media type:
E-Article
Title:
Role of Endothelin-1 in Exposure to High Altitude : Acute Mountain Sickness and Endothelin-1 (ACME-1) Study
:
Acute Mountain Sickness and Endothelin-1 (ACME-1) Study
Description:
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<jats:italic>Background—</jats:italic>
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The degree of pulmonary hypertension in healthy subjects exposed to acute hypobaric hypoxia at high altitude was found to be related to increased plasma endothelin (ET)-1. The aim of the present study was to investigate the effects of ET-1 antagonism on pulmonary hypertension, renal water, and sodium balance under acute and prolonged exposure to high-altitude–associated hypoxia.
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<jats:italic>Methods and Results—</jats:italic>
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In a double-blind fashion, healthy volunteers were randomly assigned to receive bosentan (62.5 mg for 1 day and 125 mg for the following 2 days; n=10) or placebo (n=10) at sea level and after rapid ascent to high altitude (4559 m). At sea level, bosentan did not induce any significant changes in hemodynamic or renal parameters. At altitude, bosentan induced a significant reduction of systolic pulmonary artery pressure (21±7 versus 31±7 mm Hg,
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<0.03) and a mild increase in arterial oxygen saturation versus placebo after just 1 day of treatment. However, both urinary volume and free water clearance (H
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OCl/glomerular filtration rate) were significantly reduced versus placebo after 2 days of ET-1 antagonism (1100±200 versus 1610±590 mL; −6.7±3.5 versus −1.8±4.8 mL/min,
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<0.05 versus placebo for both). Sodium clearance and segmental tubular function were not significantly affected by bosentan administration.
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<jats:italic>Conclusions—</jats:italic>
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The present results indicate that the early beneficial effect of ET-1 antagonism on pulmonary blood pressure is followed by an impairment in volume adaptation. These findings must be considered for the prevention and treatment of acute mountain sickness.
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