Clinical significance of plasma endothelin-1 level after bosentan administration in pulmonary arterial hypertension

SummaryBackgroundEndothelin (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.MethodsIn 16 PAH patients, plasma ET-1 concentration was measured at 0, 1, 3, 6, and 24 h after a single 62.5 mg 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).ResultsPlasma 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 24 h 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).ConclusionsAlthough 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.