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 function in normal and inflamed airways. We investigated the acute and chronic 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 inflammation was induced by repeated aerosolized antigen exposure, and its presence was confirmed by bronchoalveolar lavage. Acute antigen exposure in sensitized animals produced a fivefold increase in respiratory resistance over baseline that was associated with a cotemporal increase 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 in non-L-NAME-treated animals, P < 0.05). These data support the hypothesis that endogenous pulmonary NO production, as reflected by expired NO, has an important homeostatic role in acute allergic bronchoconstriction.
Mehta
S
S
Pulmonary Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Lilly
C M
CM
Rollenhagen
J E
JE
Haley
K J
KJ
Asano
K
K
Drazen
J M
JM
D000208:Acute Disease; D000280:Administration, Inhalation; D000818:Animals; D000941:Antigens / Q000276:immunology; D001991:Bronchitis / Q000378:metabolism*; D018680:Cholinergic Antagonists / Q000494:pharmacology; D002908:Chronic Disease; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009479:Neuropeptides / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011014:Pneumonia / Q000378:metabolism*; D011650:Pulmonary Alveoli; D014132:Trachea / Q000276:immunology; D014628:Vagotomy
D000941:Antigens; D018680:Cholinergic Antagonists; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester