Effect of bosentan on plasma endothelin-1 concentration in patients with pulmonary arterial hypertension.
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.


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+/-0.71 pg/ml vs 1.45+/-0.10 pg/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 8.1 h. 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.
Hiramoto
Yoshimune
Y
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Shioyama
Wataru
W
Kuroda
Tadashi
T
Masaki
Mitsuru
M
Sugiyama
Shoko
S
Okamoto
Kitaro
K
Hirota
Hisao
H
Fujio
Yasushi
Y
Hori
Masatsugu
M
Yamauchi-Takihara
Keiko
K
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure; D000077300:Bosentan; D016022:Case-Control Studies; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood / Q000187:drug effects*; D005080:Exercise Test; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011651:Pulmonary Artery / Q000503:physiopathology*; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D013449:Sulfonamides; D020097:Natriuretic Peptide, Brain; D000077300:Bosentan