Eriq Burovski, Donna Sellers, Russ Chess-Williams, Iris Lim
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Inhibition of PDE-4 and PDE-5 Differentially Modulates Isolated Porcine Urethral Contractility.
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.
期刊介绍：
The International Urogynecology Journal is the official journal of the International Urogynecological Association (IUGA).The International Urogynecology Journal has evolved in response to a perceived need amongst the clinicians, scientists, and researchers active in the field of urogynecology and pelvic floor disorders. Gynecologists, urologists, physiotherapists, nurses and basic scientists require regular means of communication within this field of pelvic floor dysfunction to express new ideas and research, and to review clinical practice in the diagnosis and treatment of women with disorders of the pelvic floor. This Journal has adopted the peer review process for all original contributions and will maintain high standards with regard to the research published therein. The clinical approach to urogynecology and pelvic floor disorders will be emphasized with each issue containing clinically relevant material that will be immediately applicable for clinical medicine. This publication covers all aspects of the field in an interdisciplinary fashion
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