Korean J Anesthesiol.  2010 Sep;59(3):196-202. 10.4097/kjae.2010.59.3.196.

Effect of ketorolac and diclofenac on the impairment of endothelium-dependent relaxation induced by reactive oxygen species in rabbit abdominal aorta

• Lee SY
• Suh JK
• Choi JH
• Jeon WJ
• Cheong MA

• KMID: 2239777
• DOI: http://doi.org/10.4097/kjae.2010.59.3.196

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% CO2 and 95% O2 at 37.5degrees C. 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 x 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 x 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 x 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.

Keyword

Catalase; Diclofenac; Endothelium; Ketorolac; Reactive oxygen species

MeSH Terms

Acetylcholine
Amitrole
Aorta, Abdominal
Arterial Pressure
Baths
Catalase
Contracts
Deferoxamine
Diclofenac
Electrolysis
Endothelium
Hydrogen Peroxide
Ketorolac
Lipid Peroxidation
Mannitol
Phenylephrine
Reactive Oxygen Species
Relaxation
Sodium Salicylate
Vasodilation
Acetylcholine
Amitrole
Catalase
Deferoxamine
Diclofenac
Hydrogen Peroxide
Ketorolac
Mannitol
Phenylephrine
Reactive Oxygen Species
Sodium Salicylate