vardenafil-dihydrochloride and Hypersensitivity

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.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Cell Degranulation; Histamine Release; Hypersensitivity; Imidazoles; Male; Mast Cells; Mice; p-Methoxy-N-methylphenethylamine; Passive Cutaneous Anaphylaxis; Peritoneal Cavity; Phosphodiesterase 5 Inhibitors; Piperazines; Rats; Sulfones; Triazines; Vardenafil Dihydrochloride