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).