ACUTE AND CHRONIC EFFECTS OF ALLERGIC AIRWAY INFLAMMATION ON PULMONARY NITRIC-OXIDE PRODUCTION

Nitric oxide (NO) is thought to be an important modulator of airway fu nction in normal and inflamed airways. We investigated the acute and c hronic effects of induced allergic airway inflammation on NO levels in mixed expired gas and NO synthase (NOS) expression in guinea pigs and the relationship between airway responses and NO production. Airway i nflammation was induced by repeated aerosolized antigen exposure, and its presence was confirmed by bronchoalveolar lavage. Acute antigen ex posure in sensitized animals produced a fivefold increase in respirato ry resistance over baseline that was associated with a cotemporal incr ease in expired NO (17 +/- 1 to 56 +/- 8 parts per billion, P < 0.01). A continuous subcutaneous infusion of nitro-L-arginine methyl ester ( L-NAME), a competitive inhibitor of NOS, markedly decreased expired NO (P < 0.01) and resulted in a significantly greater rise in resistance following antigen challenge (660 +/- 60 vs. 497 +/- 42% of baseline i n non-L-NAME-treated animals, P < 0.05). These data support the hypoth esis that endogenous pulmonary NO production, as reflected by expired NO, has an important homeostatic role in acute allergic bronchoconstri ction.