NITRIC-OXIDE MODULATES EOSINOPHIL INFILTRATION IN ANTIGEN-INDUCED AIRWAY INFLAMMATION IN RATS

The influence of nitric oxide (NO) on eosinophil infiltration into the airways was investigated in rats actively sensitized with ovalbumin. The animals were treated chronically with the NO synthase inhibitor, N -omega-Nitro-L-arginine methyl ester (L-NAME; 75 mu mol rat(-1) day(-1 )), for 4 weeks. Bronchoalveolar lavage was performed at 6, 24, 48 and 72 h after intratracheal injection of ovalbumin. Intratracheal challe nge of the sensitized rats with ovalbumin caused a significant increas e in total leucocyte infiltration in bronchoalveolar lavage fluid both 24 and 48 h post-ovalbumin injection. Neutrophils and eosinophils pea ked, respectively, at 24 h (29%) and 48 h (30%) in bronchoalveolar lav age fluid whereas the mononuclear cell did not differ significantly fr om the counts in non-sensitized rats at any time. At both 6 and 24 h p ost-ovalbumin injection, the chronic treatment of the animals with L-N AME affected neither the total nor the differential leucocyte content. However, at 48 h post-ovalbumin challenge, the total cell count was r educed by approximately 48% in the L-NAME-treated animals and this was associated with a marked inhibition (81%) of the eosinophil influx. H istological examination of the lungs from these animals (48 h post-ova lbumin challenge) also showed a prominent reduction (69.5%; P < 0.05) of the eosinophil infiltration in the respiratory segments. Our result s demonstrate that NO plays a pivotal role in the eosinophil infiltrat ion in airways of actively sensitized rats. (C) 1998 Elsevier Science B.V. All rights reserved.