Mg. Persson et al., THE PROMOTION OF PATENT AIRWAYS AND INHIBITION OF ANTIGEN-INDUCED BRONCHIAL OBSTRUCTION BY ENDOGENOUS NITRIC-OXIDE, British Journal of Pharmacology, 116(7), 1995, pp. 2957-2962
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.