Endothelial dysfunction may contribute to the extent of ischaemia/reperfusion injury. ET (endothelin)-1 receptor antagonism protects against myocardial ischaemia/reperfusion injury in animal models. The present study investigated whether oral administration of an ETA/ETB receptor antagonist protects against ischaemia/reperfusion-induced endothelial dysfunction in humans. FBF (forearm blood flow) was measured with venous occlusion plethysmography in 13 healthy male subjects. Forearm ischaemia was induced for 20 min followed by 60 min of reperfusion. Using a cross-over protocol, the subjects were randomized to oral administration of 500 mg of bosentan or placebo 2 h before ischaemia. Endothelium-dependent and -independent vasodilatation were determined by intra-brachial infusion of acetylcholine (1–10 μg/min) and nitroprusside (0.3–3 μg/min) respectively, before and after ischaemia. Compared with pre-ischaemia, the endothelium-dependent increase in FBF was significantly impaired at 15 and 30 min of reperfusion when the subjects received placebo (P<0.01). When the subjects received bosentan, the endothelium-dependent increase in FBF was not affected by ischaemia/reperfusion. Endothelium-independent vasodilatation was not affected during reperfusion compared with pre-ischaemia. The vaso-constrictor response induced by intra-arterial infusion of ET-1 was attenuated significantly by bosentan (P<0.001). The results suggest that the dual ETA/ETB receptor antagonist bosentan attenuates ischaemia/reperfusion-induced endothelial dysfunction in humans in vivo. Bosentan may thus be a feasible therapeutic agent in the treatment of ischaemia/reperfusion injury in humans.
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April 2005
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Research Article|
March 22 2005
The endothelin-1 receptor antagonist bosentan protects against ischaemia/reperfusion-induced endothelial dysfunction in humans
Felix BÖHM;
Felix BÖHM
1Department of Cardiology, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden
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Magnus SETTERGREN;
Magnus SETTERGREN
1Department of Cardiology, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden
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Adrian T. GONON;
Adrian T. GONON
1Department of Cardiology, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden
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John PERNOW
1Department of Cardiology, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden
Correspondence: Dr John Pernow (email [email protected]).
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Publisher: Portland Press Ltd
Received:
November 01 2004
Revision Received:
November 26 2004
Accepted:
December 21 2004
Accepted Manuscript online:
December 21 2004
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2005
Clin Sci (Lond) (2005) 108 (4): 357–363.
Article history
Received:
November 01 2004
Revision Received:
November 26 2004
Accepted:
December 21 2004
Accepted Manuscript online:
December 21 2004
Citation
Felix BÖHM, Magnus SETTERGREN, Adrian T. GONON, John PERNOW; The endothelin-1 receptor antagonist bosentan protects against ischaemia/reperfusion-induced endothelial dysfunction in humans. Clin Sci (Lond) 1 April 2005; 108 (4): 357–363. doi: https://doi.org/10.1042/CS20040317
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