ENDOGENOUS NITRIC-OXIDE AND ALLERGIC BRONCHIAL HYPERRESPONSIVENESS INGUINEA-PIGS

To address the role of endogenous pulmonary nitric oxide (NO) in the m odulation of airway tone, we investigated changes in expired NO levels , measured by chemiluminescence, and the effect of inhibition of NO sy nthase on inflammation-associated bronchial hyperresponsiveness in gui nea pigs. Mixed expired gas NO levels were similar at baseline in anti gen-exposed and unexposed animals and increased transiently to a simil ar degree during histamine-induced bronchoconstriction in both groups of animals [155 +/- 12% (15 +/- 1 to 23 +/- 4 ppb, P < 0.01) and 162 /- 19% (16 +/- 2 to 25 +/- 3 ppb, P < 0.01) of baseline, respectively, after administration of 30 nmol/kg histamine]. Although inhibition of NO synthase with intravenous N-G-nitro-L-arginine methyl ester (L-NAM E, 10 mg/kg) enhanced bronchial responsiveness to histamine by 30 +/- 8% in unexposed animals (P < 0.05), L-NAME did not enhance histamine r esponsiveness in antigen-exposed animals exhibiting bronchial hyperres ponsiveness 24 h after antigen exposure. Thus bronchial hyperresponsiv eness induced by repeated pulmonary antigen exposure may be associated with a transient defect in NO-related homeostatic bronchodilator acti vity.