Endogenous nitric oxide and allergic bronchial hyperresponsiveness in guinea pigs.
To address the role of endogenous pulmonary nitric oxide (NO) in the modulation of airway tone, we investigated changes in expired NO levels, measured by chemiluminescence, and the effect of inhibition of NO synthase on inflammation-associated bronchial hyperresponsiveness in guinea pigs. Mixed expired gas NO levels were similar at baseline in antigen-exposed and unexposed animals and increased transiently to a similar 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 NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) enhanced bronchial responsiveness to histamine by 30 +/- 8% in unexposed animals (P < 0.05), L-NAME did not enhance histamine responsiveness in antigen-exposed animals exhibiting bronchial hyperresponsiveness 24 h after antigen exposure. Thus bronchial hyperresponsiveness induced by repeated pulmonary antigen exposure may be associated with a transient defect in NO-related homeostatic bronchodilator activity.
Mehta
S
S
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Drazen
J M
JM
Lilly
C M
CM
D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology*; D008163:Luminescent Measurements; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors
D009569:Nitric Oxide; D006632:Histamine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester