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 o xide (NO), histamine and leukotrienes in bronchial obstruction. For th is, guinea-pigs immunised against ovalbumin were studied under anaesth esia during challenge with antigen or agonists. 2 Challenge with nebul ised antigen (0.1-1 mg) elicited dose-dependent increases in insufflat ion pressure which were abolished by combined administration of histam ine and leukotriene antagonists. 3 Challenge with nebulised antigen (0 .1-1 mg) also elicited dose-dependent increases in the concentration o f endogenous nitric oxide in the exhaled air. After an initial peak, e xhaled NO concentrations returned to pre-challenge levels. 4 The incre ase in insufflation pressure and in exhaled NO caused by ovalbumin cha llenge was inhibited by combined administration of histamine and leuko triene antagonists. 5 In non-immunised guinea-pigs, challenge of the a irways with nebulised histamine (10-1000 nmol) or leukotriene C-4 (LTC (4), 30-300 pmol) elicited dose-dependent increases in insufflation pr essure and in concentrations of endogenous NO in exhaled air. 6 The in crease in exhaled NO correlated with the increase in insufflation pres sure in response to ovalbumin, histamine and LTC(4). An inhibitor of e ndogenous 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 LTC(4). 7 The potentiati on by L-NAME of the increase in insufflation pressure in response to o valbumin or histamine was prevented by exogenous NO (20 p.p.m.) in the inhaled air. 8 The results indicate that endogenous NO has an inhibit ory effect on bronchial obstruction. Increased NO release during aller gen challenge is likely to be due to actions of histamine and leukotri enes.