PMID- 19477379
OWN - NLM
STAT- MEDLINE
DCOM- 20110216
LR  - 20181201
IS  - 1876-4738 (Electronic)
IS  - 0914-5087 (Linking)
VI  - 53
IP  - 3
DP  - 2009 Jun
TI  - Clinical significance of plasma endothelin-1 level after bosentan administration 
      in pulmonary arterial hypertension.
PG  - 374-80
LID - 10.1016/j.jjcc.2009.01.002 [doi]
AB  - 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.
FAU - Hiramoto, Yoshimune
AU  - Hiramoto Y
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, Suita, Osaka, Japan.
FAU - Shioyama, Wataru
AU  - Shioyama W
FAU - Higuchi, Kaori
AU  - Higuchi K
FAU - Arita, Yoh
AU  - Arita Y
FAU - Kuroda, Tadashi
AU  - Kuroda T
FAU - Sakata, Yasushi
AU  - Sakata Y
FAU - Nakaoka, Yoshikazu
AU  - Nakaoka Y
FAU - Fujio, Yasushi
AU  - Fujio Y
FAU - Yamauchi-Takihara, Keiko
AU  - Yamauchi-Takihara K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090220
PL  - Netherlands
TA  - J Cardiol
JT  - Journal of cardiology
JID - 8804703
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Endothelin-1)
RN  - 0 (Sulfonamides)
RN  - Q326023R30 (Bosentan)
SB  - IM
MH  - Adult
MH  - Antihypertensive Agents/*administration & dosage
MH  - Biomarkers/blood
MH  - Bosentan
MH  - Endothelin Receptor Antagonists
MH  - Endothelin-1/*blood/physiology
MH  - Female
MH  - Humans
MH  - Hypertension, Pulmonary/diagnosis/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Sulfonamides/*administration & dosage
MH  - Time Factors
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2009/05/30 09:00
MHDA- 2011/02/17 06:00
CRDT- 2009/05/30 09:00
PHST- 2008/10/23 00:00 [received]
PHST- 2009/01/07 00:00 [revised]
PHST- 2009/01/08 00:00 [accepted]
PHST- 2009/05/30 09:00 [entrez]
PHST- 2009/05/30 09:00 [pubmed]
PHST- 2011/02/17 06:00 [medline]
AID - S0914-5087(09)00041-0 [pii]
AID - 10.1016/j.jjcc.2009.01.002 [doi]
PST - ppublish
SO  - J Cardiol. 2009 Jun;53(3):374-80. doi: 10.1016/j.jjcc.2009.01.002. Epub 2009 Feb 
      20.