The promotion of patent airways and inhibition of antigen- induced bronchial obstruction by endogenous nitric oxide

摘要

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 C_4 (LTC_4, 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 LTC_4. An inhibitor of endogenous NO synthesis, N~ω-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 LTC_4. 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.