Clinical significance of plasma endothelin-1 level after bosentan administration in pulmonary arterial hypertension.
BACKGROUND
Endothelin (ET)-1 has been shown to play a significant pathogenic role in pulmonary arterial hypertension (PAH). However, the pathobiological significance of increased ET-1 concentration after administration of ET receptor antagonist in patients with PAH has not yet been fully examined.


METHODS
In 16 PAH patients, plasma ET-1 concentration was measured at 0, 1, 3, 6, and 24h after a single 62.5mg dose of bosentan, a dual ET receptor antagonist, and the peak and 24-h change in ET-1 concentration from baseline were examined. The severity of PAH was evaluated by hemodynamic parameters, 6-min walk distance, New York Heart Association (NYHA) functional class, and brain natriuretic peptide (BNP).


RESULTS
Plasma ET-1 concentration significantly increased from 1.93+/-0.12 to 3.36+/-0.18 pg/ml after bosentan administration in PAH patients (p<0.01). The peak-to-baseline ratio of ET-1 concentration after bosentan administration showed a significant positive correlation with baseline ET-1 concentration (p<0.05). After 4-week bosentan administration, NYHA functional class improved in 7 patients but was not changed in 9 patients. The optimal cut-off point of % change of ET-1 concentration at 24h for discriminating the two groups was 30%. According to this cut-off point, patients were divided into the higher (n=7) and the lower (n=9) groups. NYHA functional class did not change in the lower group, but significantly improved (p<0.01) in the higher group after 4-week bosentan administration. In addition, plasma BNP levels significantly decreased from baseline in the higher group compared with those in the lower group after 12-week bosentan administration (-44+/-11% vs. 7+/-20%, p<0.05).


CONCLUSIONS
Although the population in this study is small and heterogeneous, measurement of plasma ET-1 concentration after bosentan administration might predict the responsiveness to bosentan treatment, and be useful in the determination of effective therapy in treatment of PAH patients.
Hiramoto
Yoshimune
Y
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Shioyama
Wataru
W
Higuchi
Kaori
K
Arita
Yoh
Y
Kuroda
Tadashi
T
Sakata
Yasushi
Y
Nakaoka
Yoshikazu
Y
Fujio
Yasushi
Y
Yamauchi-Takihara
Keiko
K
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood* / Q000502:physiology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013449:Sulfonamides / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000959:Antihypertensive Agents; D015415:Biomarkers; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D013449:Sulfonamides; D000077300:Bosentan