Effects of endogenous superoxide anion and nitric oxide on cholinergic constriction of normal and hyperreactive guinea pig airways

被引:24
作者
De Boer, J [1 ]
May, F [1 ]
Pouw, H [1 ]
Zaagsma, J [1 ]
Meurs, H [1 ]
机构
[1] Univ Groningen, Ctr Pharm, Dept Mol Pharmacol, NL-9713 AV Groningen, Netherlands
关键词
D O I
10.1164/ajrccm.158.6.9711005
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
In a guinea pig model of allergic asthma, we have recently established that a deficiency of nitric oxide (MO) contributes to the Increased ex vivo responsiveness of isolated perfused tracheae to methacholine after the early asthmatic reaction at 6 h after inhalational challenge of the animals with ovalburmin aerosol. Because this deficiency could be, caused by a reaction of NO with enhanced levels of inflammation-induced superoxide anion (O-2(-)), we examined the effect of endogenous O-2(-) on the regulation of methacholine-induced constriction by NO of intact perfused tracheal tube preparations from unchallenged (control) guinea pigs and front animals 6 h after ovalbumin challenge, in the presence of the NE synthase (NOS) inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME; 100 mu M) tracheae obtained from unchallenged guinea pigs showed a 1.7-fold increase in the maximal response to intraluminally applied methacholine (p < 0.005). By contrast, the maximal airway response to methacholine was significantly decreased in the presence of the Oz scavenger superoxide dismutase (SOD; 100 U/ml) by approximately 45% (p < 0.01). The SOD-induced decrease in responsiveness to methacholine was reversed by L-NAME. Tracheal preparations obtained at 6 lip after allergen challenge showed a 5.8-fold increased responsiveness to intraluminally applied methacholine compared with controls (p < 0.001) which was not further enhanced in the presence of L-NAME, SOD had neither an effect on the increased responsiveness nor did it restore the potentiating effect of L-NAME. These results indicate that (1) in normoreactive tracheal preparations, the regulatory role of NO is partially counteracted by endogenous O-2(-), and (2) the deficiency of NO in hyperreactive tracheae obtained at 6 tp after ovalbumin challenge Is not caused by ifs reaction with O-2(-), but rather to decreased cNOS activity.
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页码:1784 / 1789
页数:6
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