Nitric oxide-induced inhibition of mouse paw edema: involvement of soluble guanylate cyclase and potassium channels

To investigate the effect of nitric oxide (NO) donors on inflammatory mouse paw edema (MPE). 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. 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. NO donors have a long-lasting anti-inflammatory effect in MPE, which involves guanylate cyclase and tetraethylammonium-sensitive potassium channels.