Reduced airway hyperresponsiveness by phosphodiesterase 3 and 4 inhibitors in guinea-pigs

Author: Germain Noella   Boichot Elisabeth   Planquois Jean-Michel   Lagente Vincent  

Publisher: Informa Healthcare

ISSN: 1466-1861

Source: Mediators of Inflammation, Vol.8, Iss.3, 1999-06, pp. : 153-157

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Abstract

THE aim of the present study was to compare the effects of selective phosphodiesterase (PDE) 3, 4 and 5 inhibitors on antigen-induced airway hyperresponsiveness in sensitized guinea-pigs. When the sensitized guinea-pigs were orally pre-treated with the selective PDE4 inhibitor, Ro 20-1724 (30 mg/kg), and studied 48 h after OA, a significant reduction (P<0.01) of the leftward shift of the dose-response curve to ACh was noted, whereas it was ineffective at the lower dose (10 mg/kg). Administration of the selective PDE3 inhibitor, milrinone (30 mg/kg) also elicited a significant reduction (P<0.01) of the airway hyperresponsiveness, whereas the PDE5 inhibitor zaprinast (30 mg/kg) was ineffective. These results show that both PDE3 and PDE4 inhibitors are able to inhibit the antigen-induced airway hyperresponsiveness in sensitized guinea-pigs and support the potential utility of selective PDE inhibitors in the treatment of asthma.