Article Text
Abstract
Objective To examine whether endogenous bradykinin mediates the endothelium-dependent vasomotor dysfunction induced by ischaemia-reperfusion injury, or the protection afforded by remote ischaemic preconditioning in vivo in man.
Design Randomised double-blind, cross-over study.
Settings Royal Infirmary of Edinburgh, Wellcome Trust Clinical Research Facility.
Patients Twenty healthy male volunteers.
Interventions Subjects were randomised to intravenous infusion of the bradykinin B2 receptor antagonist, HOE-140 (100 μg/kg), or saline placebo in a double-blind, crossover trial. Ischaemia-reperfusion injury was induced in the non-dominant arm by inflating a cuff to 200 mm Hg for 20 min in all subjects. Ischaemia-reperfusion injury was preceded by three cycles of remote ischaemic preconditioning in the dominant arm in 10 subjects.
Main outcome measures Bilateral forearm blood flow was assessed using venous occlusion plethysmography during intra-arterial infusion of acetylcholine (5–20 μg/min).
Results Acetylcholine caused vasodilatation in all studies (p<0.05) that was attenuated by ischaemia-reperfusion injury, both in the presence (p=0.0002) and absence (p=0.04) of HOE-140. Remote ischaemic preconditioning abolished the impairment of endothelium-dependent vasomotor function induced by ischaemia-reperfusion injury. HOE-140 had no effect on the protection afforded by remote ischaemic preconditioning.
Conclusions These findings do not support a major role for endogenous bradykinin, acting via the B2 kinin receptor, in the mechanism of ischaemia-reperfusion injury or the protective effects of remote ischaemic preconditioning in man.
Clinical Trial Registration Information NCT00965120 and NCT00965393.
- Bradykinin
- endothelium
- human
- receptor antagonist
- vasodilatation
- platelets
- endothelium
- endothelial function
- preconditioning
- heart failure treatment
- pulmonary arterial hypertension (PAH)
- pharmacology
- renin-angiotensin system
- intravascular ultrasound
- coronary vasomotion
- endogenous fibrinolysis
- endothelium
- platelet activation
Statistics from Altmetric.com
- Bradykinin
- endothelium
- human
- receptor antagonist
- vasodilatation
- platelets
- endothelium
- endothelial function
- preconditioning
- heart failure treatment
- pulmonary arterial hypertension (PAH)
- pharmacology
- renin-angiotensin system
- intravascular ultrasound
- coronary vasomotion
- endogenous fibrinolysis
- endothelium
- platelet activation
Footnotes
Funding This study was funded by the British Heart Foundation (PG/08/093/26020) and the Foundation Leducq. CMP received financial support from the Danish Agency for Science, Technology and Innovation, Region Midtjyllands Sundhedsvidenskabelige Forskningsfond, Det Classenske Fideicomis Jubilæumsfond, Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen's Fond, Civilingeniør Stenild Hjorth's enke Else Hjorth's Fond, The A.P. Møller Foundation for the Advancement of Medical Science, Kirsten Antonius' Mindelegat, Murermester Lauritz Peter Christensen og Hustru Kirsten Sigrid Christensens Fond, Fabrikant Karl G Andersens (Anderssons) Fond and the Institute of Clinical Medicine, University of Aarhus. RKK is supported by the Oxford NIHR Biomedical Research Centre.
Competing interests None.
Ethics approval This study was approved by Lothian Research Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.