Inhibition of PDE-4 and PDE-5 Differentially Modulates Isolated Porcine Urethral Contractility.

Abstract

Purpose/objective: This study explores the role of phosphodiesterase (PDE) inhibitors (specifically PDE-4, PDE-5 and PDE-1) in modulating the contractility of the porcine urethral smooth muscle and mucosal layers.

Methods: Using an organ bath setup, the effects of PDE inhibitors rolipram, roflumilast, sildenafil, tadalafil and vinpocetine (0.1 nM to 10 μm) on isolated porcine urethral mucosa-intact smooth muscle, mucosa-denuded smooth muscle and mucosal layers were investigated.

Results: Our results demonstrate that PDE-4 inhibitors (rolipram and roflumilast) significantly relaxed mucosa-intact urethral smooth muscle and reduced spontaneous contraction rates in the mucosal strips. Conversely, PDE-5 inhibitors (sildenafil and tadalafil) relaxed smooth muscle tissues denuded of mucosa but required exogenous source of nitric oxide (sodium nitroprusside) for effectiveness in relaxing the mucosa-intact tissues. PDE-1 inhibitor vinpocetine exhibited negligible effects.

Conclusion: The results from the study suggest a potential role of the cAMP pathway in modulating spontaneous contractions within the urethral mucosa, while the NO/cGMP pathway appears to be important in modulating urethral smooth muscle tonic contractions. These findings suggest differential roles of PDE isoenzymes in urethral tissues.