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

Cough 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.NO 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.The 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.Nitric oxide (NO) may play an essential role in regulating airway function and in the pathophysiology of inflammatory airway diseases [1]. NO is generated by NO synthase (NOS) from L-arginine in vivo [2]. NOS has three isoforms, namely neuronal NOS (nNOS: NOS-1), endothelial NOS (eNOS: NOS-3), and inducible NOS (iNOS: NOS-2) [2-6]. The former two isoforms are constitutive isozymes [7], and are assumed to regulate physiological homeostasis. The latter NOS can produce a much greater amount of NO than the constitutive forms [8]. High concentrations of NO may have not only beneficial functions (e.g. antibacterial, antiparasitic and antiviral), but also detrimental results, such as endotoxin shock [9], apoptosis [10], and pro-inflammatory effects [11,12].Exhaled nitric oxide (ENO) is at significantly elevated levels in bronchial asthma patients compared to healthy subjects [13]. Immunostaining of biopsied bronchial mucosa has shown tha