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

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Eriq Burovski, Donna Sellers, Russ Chess-Williams, Iris Lim

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Eriq Burovski: Centre for Urology Research, Faculty of Health Sciences & Medicine, Bond University, 14 University Drive, Robina, Gold Coast, QLD, 4226, Australia.
Donna Sellers: Centre for Urology Research, Faculty of Health Sciences & Medicine, Bond University, 14 University Drive, Robina, Gold Coast, QLD, 4226, Australia.
Russ Chess-Williams: Centre for Urology Research, Faculty of Health Sciences & Medicine, Bond University, 14 University Drive, Robina, Gold Coast, QLD, 4226, Australia.
Iris Lim: Centre for Urology Research, Faculty of Health Sciences & Medicine, Bond University, 14 University Drive, Robina, Gold Coast, QLD, 4226, Australia. ilim@bond.edu.au. ORCID

PMID: 40080113 DOI: 10.1007/s00192-025-06102-4

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 ��m) 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.

NO/cGMP pathway PDE inhibitors Stress urinary incontinence Urethral contractility Urethral smooth muscle cAMP pathway

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