Histamine paw edema of mice was increased and became H2-antagonist sensitive by co-injection of nitric oxide forming agents, but serotonin paw edema was decreased.
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Abstrak
Nitric oxide (NO) surprisingly caused the opposite effect on histamine and serotonin edema. The local injection of acidified nitrite (0.3-30 micrograms/paw which correspond 10 micrograms-1 mg/kg) increased histamine edema of mice up to 45 +/- 4% and suppressed serotonin edema to 90 +/- 3%. Other NO-generators (nitroprusside sodium and hydroxylamine) showed similar effects. These results were in accordance with our previous data on endogenous NO. Methylene blue (MB, 30 ng/paw which corresponds to 1 microgram/kg) suppressed histamine edema (62 +/- 3%) and increased serotonin edema (43 +/- 3%) in normal mice, being reversed by acidified nitrite. This suggests the involvement of guanosine 3',5'-cyclic monophosphate (cGMP) formation for the action of NO. Histamine edema became sensitive to H2-antagonist, cimetidine, by co-injection of 30 micrograms/paw (which corresponds to 1 mg/kg) acidified nitrite (ED50 = 30 micrograms/kg versus >> 1 mg/kg). NO seemed to modify the histamine receptor(s) or tautomeric form of histamine. NO, O2- and other oxyradicals might finely control the vascular permeability together with inflammatory mediators.