Bradykinin does not mediate remote ischaemic preconditioning or ischaemia-reperfusion injury in vivo in man. Issue 22 (26th August 2011)

• Record Type: Journal Article
• Authors: Pedersen, Christian M; Schmidt, Michael R; Barnes, Gareth; Bøtker, Hans Erik; Kharbanda, Rajesh K; Newby, David E; Cruden, Nicholas L
• Is Part Of: Heart. Volume 97:Issue 22(2011)
• Page Start: 1857
• Page End: 1861
• Publication Date: 2011-08-26
• Subjects: 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; Heart -- Diseases -- Treatment -- Periodicals; Cardiology -- Periodicals; 616.12
• DOI: 10.1136/heartjnl-2011-300323
• Languages: English
• ISSNs: 1355-6037

Abstract

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 .