title: Bradykinin Impairs and HOE 140 does not Protect Rat Hindlimb Skeletal Muscle Against Tourniquet-induced Reperfusion Injury.
abstract: BACKGROUND
  Bradykinin (BK) is used in different tissues. Dose-dependent studies have demonstrated that low doses protect against ischemia/reperfusion (I/R) injury while higher doses lead to adverse effects. Although the beneficial effects of BK infusion were observed in myocardium, its role on the I/R impact in skeletal muscle (SM) has not been fully clarified.
  
  
  OBJECTIVE
  This study was carried out to evaluate the effects of BK, administered in the hindlimbs of rats subjected to I/R.
  
  
  METHODS
  The study design included three experimental groups: Group 1 control (saline), Group 2 (bradykinin), and Group 3 (HOE 140, a BK2 receptor blocker). In all three groups, rats were subjected to hindlimb ischemia for a total of 2 h followed by continuous 4 h of reperfusion with pharmacological interventions. The methods include analysis of enzymes (lactate dehydrogenase-LDH and creatinine phosphokinase-CPK), cell membrane marker of injury (malondialdeyde-MDA), recruitment of neutrophils (myeloperoxidase-MPO), and apoptosis index (immunohistochemistry TUNEL in situ peroxidase dead end).
  
  
  RESULTS
  Except for the apoptotic index, all parameters studied were shown to be elevated in the reperfusion group intervened with BK. The blocking of BK2 receptors by HOE 140 did not affect the I/R injury.
  
  
  CONCLUSIONS
  After 2 h of total ischemia, infusion of bradykinin during 4 h of reperfusion, worsened the I/R injury in the hindlimb skeletal muscle.
authors.affiliation: a Divisions of Vascular and Endovascular Surgery and Cardiovascular Surgery, Ribeirão Preto School of Medicine, Department of Surgery and Anatomy, University of São Paulo.
authors.forename: Luciano R
authors.initials: LR
authors.lastname: Mendonça
authors.affiliation: a Divisions of Vascular and Endovascular Surgery and Cardiovascular Surgery, Ribeirão Preto School of Medicine, Department of Surgery and Anatomy, University of São Paulo.
authors.forename: Edwaldo E
authors.initials: EE
authors.lastname: Joviliano
authors.affiliation: b Ribeirão Preto School of Medicine, Department of Pathology and Legal Medicine, University of São Paulo.
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Ramalho
authors.affiliation: b Ribeirão Preto School of Medicine, Department of Pathology and Legal Medicine, University of São Paulo.
authors.forename: Leandra N Z
authors.initials: LN
authors.lastname: Ramalho
authors.affiliation: a Divisions of Vascular and Endovascular Surgery and Cardiovascular Surgery, Ribeirão Preto School of Medicine, Department of Surgery and Anatomy, University of São Paulo.
authors.forename: Paulo R B
authors.initials: PR
authors.lastname: Evora
authors.affiliation: a Divisions of Vascular and Endovascular Surgery and Cardiovascular Surgery, Ribeirão Preto School of Medicine, Department of Surgery and Anatomy, University of São Paulo.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Piccinato
mesh_terms: D000818:Animals; D017209:Apoptosis; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D065094:Bradykinin B2 Receptor Antagonists / Q000008:administration & dosage*; D003402:Creatine Kinase / Q000097:blood / Q000378:metabolism; D006614:Hindlimb / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009195:Peroxidase / Q000097:blood / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; D014665:Vasodilator Agents; D008315:Malondialdehyde; C065679:icatibant; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D003402:Creatine Kinase; D001920:Bradykinin
keywords: bradykinin; hindlimb; ischemia; ischemia–reperfusion injury; reperfusion; skeletal muscle