The influence of the PDE inhibitors on cough reflex in guinea pigs

In this study the effects of non-selective PDE inhibitors (theophylline and theobromine) and selective inhibitors of PDE 1, 3, 4 and 5 on cough, induced by citric acid, were evaluated. Inhalation of citric acid aerosol was used for cough provocation in healthy and ovalbumin-sensitized guinea pigs and the number of cough efforts was registered after visual and acoustic control by a skilled observer, with subsequent evaluation of airflow changes in a double chamber whole body plethysmograph. The pre-treatment with theophylline and theobromine (10 mg/kg b.w. intraperitoneally) decreased the number of cough efforts evoked by inhalation of citric acid aerosol (0.6 mol/l) in both healthy and ovalbumin-sensitized animals. The selective inhibitors (all 1 mg/kg b.w. intraperitoneally) of PDE1 (vinpocetin), PDE3 (cilostazol), and PDE4 (citalopram) showed antitussive effects in healthy guinea pigs. Conversely, the antitussive potential of PDE1 (vinpocetin), PDE4 (citalopram), and PDE5 (zaprinast) was observed in ovalbumin-sensitized animals. We conclude that the administration of non-selective PDE inhibitors influenced the citric acid-induced cough both in healthy and ovalbumin-sensitized guinea pigs, indicating the participation of a bronchodilating action and suppression of airway hyperreactivity in the cough suppression. With selective inhibitors, PDE4 inhibition seems to be the most effective in cough suppression, confirming its positive effects tested in chronic airway inflammatory diseases associated with bronchoconstriction and cough (Fig. 6, Ref. 27).