Effect of Bosentan on Plasma Endothelin-1 Concentration in Patients With Pulmonary Arterial Hypertension

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Background Pulmonary arterial hypertension(PAH) is a progressive disease with high mortality. An orally active dual endothelin(ET) receptor antagonist, bosentan, has been reported to improve exercise capacity and survival in patients with PAH. Plasma ET-1 concentration is known to be increased in PAH patients; however, the effect of bosentan on ET-1 concentration has not yet been investigated. Methods and Results The concentration of ET-1 after bosentan administration was examined in 7 PAH patients, including 2 primary and 5 secondary cases. They were clinically assessed by pulmonary artery pressure(PAP), 6-min walk distance(6MWD) and plasma brain natriuretic peptide(BNP) concentration. Baseline ET-1 concentration was significantly higher in patients with PAH than in normal individuals(2.19±0.71pg/ml vs 1.45±0.10pg/ml, p<0.05) and was significantly correlated with 6MWD and BNP. A single dose of 62.5 mg bosentan in patients with PAH significantly increased plasma ET-1 concentration to 2.04 times the basal concentration(p<0.01) with a peak at 8.1h. The peak to base ratio of ET-1 after bosentan administration correlated negatively with severity of PAH as assessed by PAP. Conclusions The present study is the first study to show that bosentan administration increases plasma ET-1 in patients with PAH. The response of plasma ET-1 to bosentan administration might be useful for determining the severity of PAH.
社団法人日本循環器学会の論文
2007-02-20

Effect of Bosentan on Plasma Endothelin-1 Concentration in Patients With Pulmonary Arterial Hypertension

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