title: Bradykinin and angiotensin-converting enzyme inhibition in cardioprotection.
abstract: OBJECTIVE
  To show that angiotensin-converting enzyme (ACE) inhibition potentiates subthreshold ischemic preconditioning (IPC) via the elevation of bradykinin activity, leading to a fully delayed cardioprotective response.
  
  
  METHODS
  On day 1 of the experiment, pigs were subjected to sham (group 1, controls) or IPC protocols. In groups 2 and 3, 4x5 min and 2x2 min of IPC, respectively, were elicited by occluding the left anterior descending coronary artery with percutaneous transluminal coronary angioplasty inflatable balloon catheter. Group 4 was subjected to the ACE inhibitor perindoprilate only. In group 5, the pigs were pretreated with perindoprilate (0.06 mg/kg) and then subjected to 2x2 min IPC. In group 6, intracoronary HOE 140 (a selective bradykinin B(2) receptor antagonist) was added before the perindoprilateaugmented subthreshold (2x2 min) PC stimulus. On the second day, all animals underwent 40 min left anterior descending coronary artery ligation and 3 h reperfusion, followed by infarct size analysis using triphenyl tetrazolium chloride staining.
  
  
  RESULTS
  THE RATES OF INFARCT SIZE AND RISK ZONE WERE THE FOLLOWING IN THE EXPERIMENTAL GROUPS: group 1, 42.8%; group 2,19.5% (P<0.05); group 3, ischemia/reperfusion (I/R) 33.4%; group 4, I/R 18.4% (P<0.05); group 5, I/R 31.2%; and group 6, I/R 36.3%. A significant increase of nuclear factor kappa B activation in groups 2 and 4 was seen.
  
  
  CONCLUSIONS
  Results confirm that ACE inhibitors do not give total pharmacological IPC, but they enhance the induction effect of small ischemic insults, which raises the ischemic tolerance of myocardium. It was determined that enhanced bradykinin activity leads to downstream nuclear factor kappa B activation in this model.
authors.affiliation: Department of Experimental Surgery, University of Pecs, Medical Faculty, Pécs, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Jancso
authors.forename: Mt
authors.initials: M
authors.lastname: Jaberansari
authors.forename: B
authors.initials: B
authors.lastname: Gasz
authors.forename: Z
authors.initials: Z
authors.lastname: Szanto
authors.forename: B
authors.initials: B
authors.lastname: Cserepes
authors.forename: E
authors.initials: E
authors.lastname: Röth