Isoprostanes induce plasma extravasation in rat skin.
Isoprostane E2 (8-iso PGE) and isoprostane F2 alpha (8-iso PGF) contribute to numerous vascular, proinflammatory, and nociceptive functions. The underlying mechanisms for many of their actions are still under investigation. We examined the ability of isoprostanes to promote cutaneous inflammation using the Evan's blue dye method. Our data show that 4 micrograms subcutaneously (s.c.) injected 8-iso PGE or 8-iso PGF induced plasma extravasation in glabrous rat skin. Dye extravasation was also elicited in hairy skin after injections of 8-iso PGE, but not after 8-iso PGF. Isoprostane-evoked dye extravasation can be reduced by pretreatment with both the S+ and R- isomers of the cyclooxygenase (COX)-inhibitor ibuprofen (30 mg/kg intraperitoneally), indicating perhaps a nonspecific inhibition; pretreatment with ketorolac (1 and 10 mg/kg i.v.) was without effect. Unlike isoprostane-induced cutaneous nociceptor sensitization, which is blocked in a stereospecific and dose-dependent manner by COX-inhibitors, the effect of these drugs on isoprostane-induced cutaneous plasma extravasation is less consistent. We conclude that at least a large component of the isoprostane effect on cutaneous plasma extravasation is COX-independent.
Junger
H
H
Department of Anesthesiology, University of California, San Diego 92093, USA.
Sorkin
L S
LS
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D015237:Dinoprost / Q000008:administration & dosage* / Q000031:analogs & derivatives; D015232:Dinoprostone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000209:etiology* / Q000517:prevention & control; D028441:F2-Isoprostanes; D007052:Ibuprofen / Q000008:administration & dosage; D007249:Inflammation / Q000139:chemically induced; D007279:Injections, Subcutaneous; D028421:Isoprostanes; D020910:Ketorolac / Q000008:administration & dosage; D008297:Male; D051381:Rats
D016861:Cyclooxygenase Inhibitors; D028441:F2-Isoprostanes; D028421:Isoprostanes; C075750:8-epi-prostaglandin F2alpha; D005070:Evans Blue; D015237:Dinoprost; D015232:Dinoprostone; C011987:8-isoprostaglandin E2; D007052:Ibuprofen; D020910:Ketorolac