title: Bradykinin preconditions postischemic arterial endothelial function in humans.
abstract: BACKGROUND
  Arterial endothelial dysfunction is an important mechanism of tissue injury caused by ischemia-reperfusion (I/R). Earlier studies of I/R have shown that intracoronary preinfusion with 2.5-5 microg/mL bradykinin (BK) could alleviate the postischemic myocardial damage. Using an experimental human model of I/R, we investigated whether preceding infusion with BK could prevent the I/R-induced arterial endothelial dysfunction.
  
  
  METHODS
  The left radial artery (LRA) from 16 healthy male adults, 18 to 30 years old, was submitted to I/R by completely occluding the left brachial artery with a pressure tourniquet for 20 minutes (ischemia), followed by its release (reperfusion). Prior to I/R, half of the subjects were randomly assigned to receive either BK (5 microg/mL) or saline, both being infused into the left brachial artery (0.5 mL/min, 10 min). The infusion was followed by a 10-minute drug-free period. The endothelial function of the LRA was studied by measuring the flow-mediated dilation (FMD) at baseline (prior to drug infusion), and at 15 minutes of reperfusion. In addition, baseline radial artery diameter, plasma nitrate, and von Willebrand factor were measured at these time points, and immediately before I/R (pre-I/R).
  
  
  RESULTS
  BK had no effect on the pre-I/R plasma nitrate (p > 0.5 vs. saline) and diameter of LRA (p > 0.5 vs. baseline). At 15 minutes of reperfusion, FMD was significantly decreased in the saline group as compared to baseline (absolute dilation: 0.08 +/- 0.03 vs. 3.02 +/- 0.8 mm, respectively, p < 0.01; percentage dilation: 3 +/- 0.6 vs. 8 +/- 0.6%, respectively, p < 0.001), but it remained unaffected in the BK group (absolute dilation: 3.06 +/- 0.9 vs. 3.27 +/- 0.8 mm, respectively, p > 0.5; percentage dilation: 7 +/- 0.7 vs. 8 +/- 0.8%, respectively, p > 0.5). A similar trend was observed with regard to plasma nitrate, which remained unchanged in the BK group (37.01 +/- 4.14 vs. 39.14 +/- 4.49 micromol/L, p > 0.5) but decreased in the saline group (35.91 +/- 3.03 vs. 28.91 +/- 2.81 micromol/L, p < 0.1).
  
  
  CONCLUSIONS
  Infusion of BK could protect the arterial endothelial function against I/R injury in humans, possibly in part by preserving the endothelial NO availability. The findings support the use of BK in the prevention of tissue injury due to I/R and might reveal an additional mechanism whereby ACE inhibitors exert their preconditioning effects on myocardium.
authors.affiliation: Division of Pediatric Cardiology, University Hospital Lund, Sweden. Pietru.Liuba@pedi.lu.se
authors.forename: Petru
authors.initials: P
authors.lastname: Liuba
authors.forename: Satish
authors.initials: S
authors.lastname: Batra
authors.forename: Erkki
authors.initials: E
authors.lastname: Pesonen
authors.forename: Olof
authors.initials: O
authors.lastname: Werner
mesh_terms: D000293:Adolescent; D000328:Adult; D001920:Bradykinin / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D007261:Infusions, Intra-Arterial; D019194:Ischemic Preconditioning; D008297:Male; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D017534:Radial Artery / Q000503:physiopathology; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000008:administration & dosage*; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D009566:Nitrates; D009573:Nitrites; D014665:Vasodilator Agents; D014841:von Willebrand Factor; D001920:Bradykinin