Nitric oxide and the cyclic nucleotide monophosphates cAMP and cGMP have a role in control of the micturition process and hence, are suggested to be involved in the pathophysiology of storage and voiding disorders. Phosphodiesterase enzymes (PDEs) hydrolyse cAMP and cGMP. Inhibition of PDEs increases cAMP and cGMP levels and relaxes urinary bladder smooth musculature. Although many preclinical studies have been conducted, to date, only PDE1 and PDE5 inhibitors have been tested clinically for the management of storage and voiding disorders. Treatment with PDE1 inhibitors might improve micturition frequency in patients with overactive bladder, whereas inhibition of PDE5 improves lower urinary tract symptoms in men, either with or without BPH and erectile dysfunction (ED). Furthermore, the combination of a PDE5 inhibitor and an α-adrenoceptor antagonist has superior efficacy to monotherapy with either agent. However, the role of PDE5 inhibitors in the treatment of women with detrusor overactivity remains unclear. The clinical application of agents that inhibit other PDEs, including PDE4, also certainly merits scientific attention. PDE inhibitors seem likely to become a valuable alternative treatment for patients with storage and voiding disorders in the future.
Phosphodiesterases (PDEs) hydrolyse cAMP and cGMP, and are thought to have a crucial role in bladder physiology
Inhibition of PDEs raises cAMP and cGMP levels and relaxes urinary bladder muscles
Although PDEs 1–5 and 7–9 occur in the human urinary bladder, only PDE1 and PDE5 inhibitors have been clinically tested for the treatment of storage and voiding disorders
PDE1 inhibition improves micturition frequency
PDE5 inhibition alleviates lower urinary tract symptoms in men, including those with and without BPH and erectile dysfunction
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The authors declare no competing financial interests.
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Rahnama'i, M., Ückert, S., Hohnen, R. et al. The role of phosphodiesterases in bladder pathophysiology. Nat Rev Urol 10, 414–424 (2013). https://doi.org/10.1038/nrurol.2013.101
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