Cyclic nucleotides, such as cAMP and cGMP, play a protective role in the modulation of the activity of some inflammatory cells in allergic disorders. Their intracellular concentrations are tightly regulated by the
phosphodiesterases (
PDEs). The protective efficacy of the selective
PDE5 inhibitor vardenafil against mast-cell-mediated
allergic reactions in murine models has been investigated.
Compound 48/80 was used as a direct mast cell degranulator to induce
anaphylaxis.
Vardenafil (administered orally at 5, 10, 20, 40, and 80 mg/kg body mass) significantly (P < 0.05, n = 12) increased protection against
compound-48/80-induced
anaphylaxis in mice to 33.33%, 66.67%, 66.67%, 83.33%, and 66.67% respectively compared with the control (vehicle). In passive cutaneous anaphylaxis (PCA) in rats,
vardenafil (10 mg/kg body mass) significantly (P < 0.05, n = 6) decreased
Evans' blue dye extravasation (4.6-fold). Pre-incubation of isolated rat peritoneal mast cells (RPMCs) with
vardenafil (10 and 100 μmol/L) significantly (P < 0.05, n = 6) reduced
compound-48/80-induced histamine release by 2.8- and 3-fold, respectively. Moreover, histamine release by immunogenic stimulation of sensitized RPMCs by egg
albumin significantly declined following pre-incubation with
vardenafil (10 and 100 μmol/L) by 1.94- and 1.99-fold, respectively. In conclusion, inhibition of PDE5 by
vardenafil ameliorated immunologic and non-immunologic mast-cell-mediated
allergic reactions and reduced histamine release, providing evidence for the potential
anti-allergic properties of
vardenafil.