Nitric oxide-induced inhibition of mouse paw edema: involvement of soluble guanylate cyclase and potassium channels.
OBJECTIVE
To investigate the effect of nitric oxide (NO) donors on inflammatory mouse paw edema (MPE).


METHODS
Mice previously treated with sodium nitroprusside (SNP; 1.5, 5 and 10 micromol/kg) or S-nitroso-N-acetyl-DL-penicillamine (SNAP; 7, 14 and 28 micromol/kg) were injected with inflammatory mediators in the paw. Paw edema, myeloperoxidase activity and vascular dye leakage were measured.


RESULTS
Pre-treatment with SNP and SNAP (4 h or 12 h) reduced (approximately 50%) MPE induced by carrageenan, dextran sulfate, bradykinin and histamine but not by serotonin. Pre-treatment with SNP also inhibited carrageenan-induced increases in myeloperoxidase activity and vascular dye leakage. Methylene blue blocked the SNP-induced reduction in MPE when injected 30 min before or 2 h after SNP, but not 4 or 6 h after the NO donor. Tetraethylammonium blocked the SNP-induced reduction in MPE if injected 30 min before or 2, 4 or 6 h after SNP.


CONCLUSIONS
NO donors have a long-lasting anti-inflammatory effect in MPE, which involves guanylate cyclase and tetraethylammonium-sensitive potassium channels.
Fernandes
D
D
Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil,
Da Silva-Santos
J E
JE
Assreuy
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002351:Carrageenan / Q000008:administration & dosage / Q000494:pharmacology; D016264:Dextran Sulfate / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D007279:Injections, Subcutaneous; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D013997:Time Factors
D020030:Nitric Oxide Donors; D015221:Potassium Channels; C110881:S-nitro-N-acetylpenicillamine; D009599:Nitroprusside; D009569:Nitric Oxide; D012701:Serotonin; D006632:Histamine; D002351:Carrageenan; D016264:Dextran Sulfate; D009195:Peroxidase; D006162:Guanylate Cyclase; D010396:Penicillamine; D001920:Bradykinin