Reduced airway hyperresponsiveness by phosphodiesterase 3 and 4 inhibitorsin guinea-pigs

THE aim of the present study was to compare the effects of selective phosph odiesterase (PDE) 3, 4 and 5 inhibitors on antigen-induced airway hyperresp onsiveness in sensitized guinea-pigs, When the sensitized guinea-pigs a ere orally pre-treated with the selective PDE4 inhibitor, Ro 20-1724 (30 mg/kg ), and studied 48h after OA, a significant reduction (P<0.01) of the leftwa rd shift of the dose-response curve to ACh was noted, whereas it was ineffe ctive at the lon er dose (10 mg/kg), Administration of the selective PDE3 i nhibitor, milrinone (30 mg/kg) also elicited a significant reduction (P<0.0 1) of the airway hyperresponsiveness, whereas the PDES inhibitor zaprinast (30 mg/kg) was ineffective. These results show that both PDES and PDE4 inhi bitors are able to inhibit the antigen-induced airway hyperresponsiveness i n sensitized guinea-pigs and support the potential utility of selective PDE inhibitors in the treatment of asthma.