The promotion of patent airways and inhibition of antigen-induced bronchial obstruction by endogenous nitric oxide.
1. The aim of the present study was to investigate the role of nitric oxide (NO), histamine and leukotrienes in bronchial obstruction. For this, guinea-pigs immunised against ovalbumin were studied under anaesthesia during challenge with antigen or agonists. 2. Challenge with nebulised antigen (0.1-1 mg) elicited dose-dependent increases in insufflation pressure which were abolished by combined administration of histamine and leukotriene antagonists. 3. Challenge with nebulised antigen (0.1-1 mg) also elicited dose-dependent increases in the concentration of endogenous nitric oxide in the exhaled air. After an initial peak, exhaled NO concentrations returned to pre-challenge levels. 4. The increase in insufflation pressure and in exhaled NO caused by ovalbumin challenge was inhibited by combined administration of histamine and leukotriene antagonists. 5. In non-immunised guinea-pigs, challenge of the airways with nebulised histamine (10-1000 nmol) or leukotriene C4 (LTC4, 30-300 pmol) elicited dose-dependent increases in insufflation pressure and in concentrations of endogenous NO in exhaled air. 6. The increase in exhaled NO correlated with the increase in insufflation pressure in response to ovalbumin, histamine and LTC4. An inhibitor of endogenous NO synthesis, N omega-nitro-L-arginine methylester (L-NAME, 30 mg kg-1 i.v.) abolished NO exhalation, and markedly augmented the airway responses to ovalbumin, histamine, or LTC4. 7. The potentiation by L-NAME of the increase in insufflation pressure in response to ovalbumin or histamine was prevented by exogenous NO (20 p.p.m.) in the inhaled air. 8. The results indicate that endogenous NO has an inhibitory effect on bronchial obstruction. Increased NO release during allergen challenge is likely to be due to actions of histamine and leukotrienes.
Persson
M G
MG
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Friberg
S G
SG
Gustafsson
L E
LE
Hedqvist
P
P
D000402:Airway Obstruction / Q000276:immunology / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001982:Bronchial Diseases / Q000276:immunology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D006168:Guinea Pigs; D006632:Histamine / Q000502:physiology*; D015289:Leukotrienes / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*
D000941:Antigens; D015289:Leukotrienes; D009569:Nitric Oxide; D006632:Histamine