Involvement of guanylate cyclase and potassium channels on the delayed phase of mouse carrageenan-induced paw oedema.
Previous studies from this laboratory have shown that administration of nitric oxide (NO) donors reduces the early phase (which peaks at 4 h) of carrageenan-induced paw oedema. The aim of this study was to investigate the influence of NO donors on the delayed phase of the mouse paw oedema, which peaks 48 h after carrageenan injection. Treatment of animals with sodium nitroprusside (1.5, 5 and 10 micromol/kg, subcutaneously (s.c.)) 8 h after the subplantar carrageenan injection (300 microg/paw), reduced ( approximately 50%) the delayed phase of paw oedema and the delayed increase in plasma leakage, as assessed by Evans Blue extravasation. Two other NO donors, S-nitroso-N-acetyl-dl-penicillamine (SNAP) or glyceril trinitrate (both at 28 micromol/kg) yielded an inhibition in paw oedema similar to that of sodium nitroprusside. NO-induced inhibition of the delayed phase of paw oedema was reversed when animals were treated with 1H-[1,2,4]-oxadiazolo-[4,3-a]quinoxalin-1 (ODQ, a soluble guanylate cyclase inhibitor, 11 micromol/kg, s.c.) or with tetraethylammonium (TEA, a nonselective potassium channel blocker, 300 micromol/kg, s.c.), 30 min before the prophylactic dose of sodium nitroprusside. In conclusion, our results show that a brief exposure to NO donors, even when made several hours after the inflammatory reaction has been triggered, is still able to cause an important reduction on the delayed phase of carrageenan-induced mouse paw oedema and fluid leakage. Moreover, this long-lasting NO antiinflammatory effect appears to be dependent on guanylate cyclase and potassium channels.
Department of Pharmacology, Universidade Federal de Santa Catarina, University Campus, Trindade, Biological Sciences Centre, Block "D", Florianopolis-SC-88049-900-Brazil.
Daniel
D
Fernandes
Jamil
J
Assreuy
D000818:Animals; D002351:Carrageenan / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D005552:Forelimb; D006162:Guanylate Cyclase / Q000502:physiology*; D051379:Mice; D015221:Potassium Channels / Q000502:physiology*; D013997:Time Factors
D015221:Potassium Channels; D002351:Carrageenan; D006162:Guanylate Cyclase