Vascular permeabilization by intravenous arachidonate in the rat peritoneal cavity: antagonism by antioxidants.
Arachidonic acid was investigated for its vascular permeabilizing potential in the rat peritoneal cavity and for its mechanism of action. The antagonistic potential of antioxidants (vitamin E, vitamin C and troxerutin) was also evaluated. Vascular permeability was equated to the rate of extravasation of Evans blue dye from plasma into the peritoneal cavity. Baseline permeability was linear up to 2 h, with a rate constant (k) of 0.0031+/-0.0007 h(-1). Intravenous arachidonate (from 30 microg/kg to 3 mg/kg) induced an immediate, dose-related and significant increase in permeability (ranging from 80% to 150%), which was comparable to the effect induced by similar doses of serotonin. Aspirin (10 mg/kg) reduced the arachidonate-induced permeability by 75%, but interestingly neither the stable thromboxane A(2) receptor agonist U46619 (prostaglandin H(2) endoperoxide epoxymethane) nor prostacyclin was able to increase peritoneal vascular permeability. In contrast, the permeabilizing action of arachidonic acid was very sensitive to antioxidant agents. Thus, vitamin C and the flavonoid compound troxerutin (100 mg/kg) fully abolished arachidonate-induced permeability, whereas vitamin E had only a partial effect (40-100% inhibition). In conclusion, intravenous administration of arachidonic acid strongly enhanced peritoneal vascular permeability in the rat, apparently via free radical generation. This rat peritoneal model can be used to evaluate the in vivo antinflammatory potential of antioxidant drugs.
Alvarez-Guerra
Miriam
M
INSERM U400, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Cédex, Créteil, France.
Hannaert
Patrick
P
Hider
Hamida
H
Chiavaroli
Carlo
C
Garay
Ricardo P
RP
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D004396:Coloring Agents; D004195:Disease Models, Animal; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006896:Hydroxyethylrutoside / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D010529:Peritoneal Cavity / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013997:Time Factors; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology
D000975:Antioxidants; D004396:Coloring Agents; D006896:Hydroxyethylrutoside; D017382:Reactive Oxygen Species; D014810:Vitamin E; D016718:Arachidonic Acid; D005070:Evans Blue; C005865:troxerutin; D001205:Ascorbic Acid