title: Effect of ketorolac and diclofenac on the impairment of endothelium-dependent relaxation induced by reactive oxygen species in rabbit abdominal aorta.
abstract: BACKGROUND
  Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in endothelium. We studied the influences of ketorolac and diclofenac on ROS effects using the endothelium of rabbit abdominal aorta.
  
  
  METHODS
  Isolated rabbit aortic rings were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution bubbled with 5% CO(2) and 95% O(2) at 37.5℃. After being stimulated to contract with phenylephrine (PE, 10(-6) M), changes in arterial tension were recorded following the cumulative administration of acetylcholine (ACh, 3 × 10(-8) to 10(-6) M). The percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS, generated by electrolysis of K-H solution, were used as the control and experimental values, respectively. The aortic rings were pretreated with ketorolac or diclofenac at the same concentrations (10(-5) M to 3 × 10(-4) M), and the effects of these agents were compared with the effects of ROS scavengers: catalase, mannitol, sodium salicylate and deferoxamine and the catalase inhibitor, 3-amino-1,2,4-triazole (3AT).
  
  
  RESULTS
  Both ketorolac and diclofenac maintained endothlium-dependent relaxation induced by ACh in a dose-related manner inspite of ROS attack (P < 0.05 vs. control value). The 3AT pretreated ketorolac (3 × 10(-3) M) group was decreased more significantly than un-pretreated ketorolac (P < 0.05).
  
  
  CONCLUSIONS
  These findings suggest that ketorlac and diclofenac preserve the endothelium-dependent vasorelaxation against the attack of ROS, in a concentration-related manner. One of the endothelial protection mechanisms of ketorolac may be hydrogen peroxide scavenging.
authors.affiliation: Department of Anesthesiology and Pain Medicine, College of Medicine, Jeju University, Jeju, Korea.
authors.forename: Seung Yoon
authors.initials: SY
authors.lastname: Lee
authors.forename: Jung Kook
authors.initials: JK
authors.lastname: Suh
authors.forename: Jin Hwa
authors.initials: JH
authors.lastname: Choi
authors.forename: Woo Jae
authors.initials: WJ
authors.lastname: Jeon
authors.forename: Mi Ae
authors.initials: MA
authors.lastname: Cheong