Improvement of plasma endothelin-1 and nitric oxide in patients with systemic sclerosis by bosentan therapy.
The aim of this study was to evaluate the effects of bosentan on plasma endothelin-1 (ET-1) and nitric oxide (NO) as pulmonary hypertension (PH)-associated biochemical markers in patients with systemic sclerosis (SSc). Twenty-four SSc patients receiving bosentan for 24 weeks were registered in this prospective observational study. Ten patients were complicated with clinically suspected PH. Plasma levels of ET-1 and NO were assessed at baseline and after 24 weeks of treatment in SSc patients and in 15 healthy controls. Plasma levels of ET-1 and NO at baseline were significantly higher in SSc patients than in healthy controls (p < 0.000), and they were also significantly higher in SSc patients with PH than in those without PH (p < 0.01). Plasma ET-1 levels were significantly decreased after 24 weeks of bosentan therapy (p < 0.0001), and ET-1 levels of SSc patients with PH decreased to a level comparable to that in patients without PH. In the 10 SSc patients with PH, changes in plasma ET-1 levels during the 24 weeks of the study were significantly larger in the 5 patients whose functional class (FC) improved than in the 5 patients whose FC was unchanged (p < 0.05). Plasma NO levels were also slightly decreased in SSc patients after 24 weeks of bosentan therapy. Plasma ET-1 levels could reflect the presence and severity of PH in SSc patients. Additionally, changes in plasma ET-1 levels may indicate the response to bosentan therapy in SSc patients with PH.
Department of Public Health, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan, shin-ya@hotmail.co.jp.
Shin-ya
SY
Kawashiri
Yukitaka
Y
Ueki
Kaoru
K
Terada
Satoshi
S
Yamasaki
Kiyoshi
K
Aoyagi
Atsushi
A
Kawakami
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D000077300:Bosentan; D019332:Endothelin-1 / Q000097:blood*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D011446:Prospective Studies; D012595:Scleroderma, Systemic / Q000150:complications* / Q000175:diagnosis; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D015415:Biomarkers; D019332:Endothelin-1; D013449:Sulfonamides; D009569:Nitric Oxide; D000077300:Bosentan