NITRIC-OXIDE INHIBITS NEUTROPHIL INFILTRATION IN THE REVERSE PASSIVE ARTHUS REACTION IN RAT SKIN

The role of nitric oxide (NO) in the reverse passive Arthus reaction e licited in the rat skin has been studied. The reverse passive Arthus r eaction was modulated by test compounds given by intradermal injection in combination with anti-bovine serum albumin antibody. L-arginine (1 .5-15 mu mol/site) and the NO donor [1-hydroxy-2-oxo-3,3-bis (3-amonoe thyl)-1-triazene] (NOC-18; 1-10 mu mol/site) both significantly reduce d neutrophil infiltration and increased plasma leakage. The NO scaveng er haemoglobin (30 and 100 mu mol/site) did not affect oedema formatio n but increased neutrophil infiltration and attenuated the effects of L-arginine. The non-selective nitric oxide synthase inhibitors NG-nitr o-L-arginine methyl ester (0.3-100 nmol/site) and NG-monomethyl-L-argi nine (0.3-100 nmol/site) or the relatively selective inhibitors of the inducible NO synthase aminoguanidine (30-1000 nmol/site) and S-methyl thiourea (3-1000 nmol/site) significantly reduced plasma leakage when given at high doses. Furthermore all these inhibitors exhibited a dose -related biphasic effect on neutrophil infiltration which was signific antly increased by low doses and reduced by high doses, while intermed iate doses had no effect. Phenylpropanolamine, a sympathomimetic vasoc onstrictor (15-60 mu mol/site), dose-dependently reduced both oedema f ormation and neutrophil infiltration. These results provide evidence f or a relevant role of NO as a modulator of rat dermal reverse passive Arthus reaction and suggest that at the vascular level NO controls pri marily the interaction between leucocyte and endothelial cell rather t han the vascular permeability.