NITRIC-OXIDE MODULATES CARDIAC AND MAST-CELL ANAPHYLAXIS

Anaphylaxis in the isolated guinea-pig heart was associated with a sud den release of histamine with a long-lasting release of nitrite (NO2-) , an oxidation product of NO. N-G-monomethyl-L-arginine (MeArg, 300 mu M) increased the severity of cardiac anaphylaxis, as shown by the dec rease in the coronary flow and by a prolonged duration of antigen-indu ced arrhythmias. Concomitantly, MeArg increased the release of histami ne while decreasing the release of nitrite. Sodium nitroprusside (NaNP , 10(-5)-10(-4) M) reduced the severity of cardiac anaphylaxis by incr easing coronary flow and shortening the duration of antigen-induced ar rhythmias. Concomitantly, NaNP decreased the release of histamine whil e increasing the release of nitrite. In mast cells isolated from activ ely sensitized guinea-pigs, the release of histamine elicited by speci fic antigen was increased by MeArg and decreased by NaNP. In conclusio n, endogenous and exogenous NO antagonizes the effect of vasoconstrict or mediators released after antigen challenge and plays a protective r ole in anaphylactic reactions ''in vitro''.