Involvement of nitric oxide (NO) in cough reflex sensitivity between non-sensitized and OVA-sensitized guinea pigs

Akihiro Hori,Masaki Fujimura,Akira Tokuda,Noriyuki Ohkura

doi:10.1186/1745-9974-7-5

Abstract

BackgroundExhaled nitric oxide (ENO) is elevated in bronchial asthma patients, and inhaled corticosteroid therapy lowers the elevated ENO levels in such patients. ENO appears to be an inflammatory marker, but its role in the pathophysiology of cough remains unclear. This study aimed to elucidate the relationship between NO and increased cough reflex sensitivity induced by allergic airway reactions.MethodsCough reflex sensitivity to inhaled capsaicin was observed under NO depletion caused by NO synthase (NOS) inhibitors in non-sensitized and ovalbumin (OVA)-sensitized guinea pigs. The bronchoalveolar lavage fluid (BALF) was analyzed in an NO depletion setting using the inducible NOS (iNOS) inhibitor ONO1714 in OVA-sensitized guinea pigs.ResultsNO depletion by the non-selective NOS inhibitor L-NAME suppressed cough reflex sensitivity in non-sensitized guinea pigs and OVA-induced increase in cough reflex sensitivity in sensitized guinea pigs; however, iNOS inhibition caused by ONO1714 partially suppressed the OVA-induced increase in cough reflex sensitivity, but not the normal cough response in non-sensitized guinea pigs. ONO1714 did not change BAL cell components in OVA-sensitized guinea pigs.ConclusionsThe results suggest that NO may be involved not only in the normal cough reflex circuit, but also in the OVA-induced increase in cough reflex sensitivity, possibly via a different mechanism of action. Further studies are needed to clarify the precise mechanism.

Highlights

Exhaled nitric oxide (ENO) is elevated in bronchial asthma patients, and inhaled corticosteroid therapy lowers the elevated ENO levels in such patients
ENO and eosinophil counts in bronchoalveolar lavage fluid (BALF) were significantly higher in OVA-sensitized guinea pigs compared to non-sensitized guinea pigs (Figure 6, Figure 7, Table 1), suggesting that the OVA-induced increase in cough reflex sensitivity may be associated with increased NO production and eosinophil accumulation
The present study demonstrated that ENO from OVAsensitized guinea pigs was significantly higher than that from non-sensitized guinea pigs; cough reflex sensitivity to inhaled capsaicin was significantly higher as well, as was shown in our previous study [23]

Summary

Introduction

Exhaled nitric oxide (ENO) is elevated in bronchial asthma patients, and inhaled corticosteroid therapy lowers the elevated ENO levels in such patients. NOS has three isoforms, namely neuronal NOS (nNOS: NOS1), endothelial NOS (eNOS: NOS-3), and inducible NOS (iNOS: NOS-2) [2,3,4,5,6] The former two isoforms are constitutive isozymes [7], and are assumed to regulate physiological homeostasis. High concentrations of NO may have beneficial functions (e.g. antibacterial, antiparasitic and Exhaled nitric oxide (ENO) is at significantly elevated levels in bronchial asthma patients compared to healthy subjects [13]. Glucocorticoids inhibit expression of iNOS, but not of cNOS, in vascular endothelial cells [14] These findings indicate that the augmentation of ENO results from increased iNOS expression in the airway of bronchial asthma patients. De Diego et al reported that ENO levels in cough variant asthma patients were similar to those in bronchial asthma patients [16]

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