Nitric oxide reverses endotoxin-induced inflammatory hyperalgesia via inhibition of prostacyclin production in mice.
We examined whether nitric oxide (NO), derived from constitutive NO synthase (NOS) and/or inducible NOS (iNOS), could contribute to endotoxin-induced inflammatory hyperalgesia via interacting with nuclear factor-kappaB (NF-kappaB), inducible cyclooxygenase (COX-2) and/or polyADP-ribose synthase (PARS). Injection of endotoxin (10 mg kg(-1), i.p.) to mice elicited hyperalgesia, determined by hot plate test, which is prevented by NO precursor (L-arginine), cNOS/iNOS inhibitor (N(G)-nitro-L-arginine methyl ester; L-NAME), NF-kappaB inhibitor (N-acetylserotonin), COX inhibitor (indomethacin), COX-2 inhibitor (DFU) and PARS inhibitor (3-aminobenzamide). Endotoxin caused a decrease in serum nitrite levels prevented by N-acetylserotonin, L-arginine, indomethacin, DFU or 3-aminobenzamide. Endotoxin increased serum 6-keto-PGF(1alpha) levels diminished by L-arginine or aminoguanidine (iNOS inhibitor). L-Arginine, L-NAME, aminoguanidine, DFU or 3-aminobenzamide prevented endotoxin-induced decrease in heart, lungs, kidneys and brain nitrite and malonedialdehyde levels and myeloperoxidase activity. In conclusion, NO reverses endotoxin-induced inflammatory hyperalgesia via inhibition of prostacyclin production, and also contributes to the analgesic effect of NF-kappaB, COX or PARS inhibitors.
Tunctan
B
B
Department of Pharmacology, Faculty of Pharmacy, Yenisehir Campus, Mersin University, Mersin 33169, Turkey. btunctan@yahoo.com
Ozveren
E
E
Korkmaz
B
B
Buharalioglu
C K
CK
Tamer
L
L
Degirmenci
U
U
Atik
U
U
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors; D044062:Prostaglandins I / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D011506:Proteins / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D044062:Prostaglandins I; D011506:Proteins; D011064:Poly Adenosine Diphosphate Ribose; D009569:Nitric Oxide; D008315:Malondialdehyde; D015121:6-Ketoprostaglandin F1 alpha; D009195:Peroxidase; D019001:Nitric Oxide Synthase