No effects of bosentan on microvasculature in patients with limited cutaneous systemic sclerosis.
The endothelium-derived vasoconstrictor molecule endothelin-1 (ET-1) has been suggested to play a role in the pathogenesis of Raynaud's phenomenon (RP) and systemic sclerosis (SSc). We studied the effect of bosentan on microvascular structure and function in patients with RP secondary to limited cutaneous SSc in a mechanistic pilot study. In this single center, open study, 15 patients with limited cutaneous SSc were treated with bosentan for 16 weeks with a follow-up period of 4 weeks. Changes in microvascular structure and function were studied with assessment of vasodilatory microvascular responses using laser Doppler fluxmetry combined with iontophoresis, capillary permeability using fluorescence videomicroscopy, nailfold capillary microscopy, and serological markers of endothelial activation. No significant changes were seen in vasodilator responses to acetylcholine and sodium nitroprusside following bosentan treatment. No effect was noted on capillary permeability during treatment. The number of nailfold capillaries remained unchanged. The endothelial activation marker vascular cell adhesion molecule did not change during treatment, but levels of thrombomodulin significantly decreased after 12 weeks of treatment. Bosentan did not induce significant changes in vasodilator responses, capillary permeability, and capillary density during treatment, so no evidence was obtained for structural improvement of microvascular structure and function in this short-time mechanistic pilot study in patients with lcSSc.
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands. M.Hettema@ziekenhuis-mst.nl
Martha E
ME
Hettema
Dan
D
Zhang
Ymkje
Y
Stienstra
Andries J
AJ
Smit
Hendrika
H
Bootsma
Cees G M
CG
Kallenberg
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D020678:Microscopic Angioscopy / Q000379:methods; D008875:Middle Aged; D009262:Nails / Q000098:blood supply; D010045:Outpatients; D010865:Pilot Projects; D011928:Raynaud Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D045745:Scleroderma, Limited / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D007166:Immunosuppressive Agents; D013449:Sulfonamides; D000077300:Bosentan