title: Bradykinin does not mediate remote ischaemic preconditioning or ischaemia-reperfusion injury in vivo in man.
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.
  
  
  METHODS
  Randomised double-blind, cross-over study.
  
  
  METHODS
  Royal Infirmary of Edinburgh, Wellcome Trust Clinical Research Facility.
  
  
  METHODS
  Twenty healthy male volunteers.
  
  
  METHODS
  Subjects were randomised to intravenous infusion of the bradykinin B(2) 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.
  
  
  METHODS
  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 B(2) kinin receptor, in the mechanism of ischaemia-reperfusion injury or the protective effects of remote ischaemic preconditioning in man.
  
  
  BACKGROUND
  NCT00965120 and NCT00965393.
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, UK. christian.m.pedersen@ki.au.dk
authors.forename: Christian M
authors.initials: CM
authors.lastname: Pedersen
authors.forename: Michael R
authors.initials: MR
authors.lastname: Schmidt
authors.forename: Gareth
authors.initials: G
authors.lastname: Barnes
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Kharbanda
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Cruden
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000328:Adult; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism*; D065168:Bradykinin Receptor Antagonists; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects; D005542:Forearm / Q000098:blood supply / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D019194:Ischemic Preconditioning; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D010991:Plethysmography; D011379:Prognosis; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D012965:Sodium Chloride / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D065168:Bradykinin Receptor Antagonists; D014665:Vasodilator Agents; D012965:Sodium Chloride; C065679:icatibant; D000109:Acetylcholine; D001920:Bradykinin