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Research Type
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Pure and Applied Science / Translational |
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Keywords
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Urothelial signalling Afferent sensitisation Bladder relaxation |
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Target Audience
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Urology, Urogynaecology, Basic Science |
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Aims and Objectives
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PDE5 inhibitors (e.g., tadalafil, sildenafil) may be used to treat lower urinary tract symptoms (LUTS). They are proposed to work by increasing protein kinase G (PKG) signalling via nitric oxide (NO•)-induced activation of soluble guanylate cyclase (sGC). This alters the functional behaviour of targets including: urothelial cells, afferent and efferent nerves, as well as detrusor smooth muscle, by mechanisms incompletely understood. sGC activators (e.g., BAY-582667) also increase PKG activity but, crucially, can do so in the absence of NO• which can occur if nitrergic nerves are damaged. Our aims are to discuss the cellular targets, mechanisms of actions and therapeutic relevance of PDE5 inhibitors and sGC activators to treat LUTS.
Learning Objectives - Provide up-to-date information on the clinical relevance of PDE5 inhibitors and sGC activators for the treatment of LUTS. As BAY-582667 has passed phase 1 safety trials for non-urological pathologies, sGC activators have high translational/clinical relevance for patients with LUTS who are unresponsive to PDE5 inhibitors.
- Discuss the putative mechanisms of actions by which PDE5 inhibitors and sGC activators treat LUTS by: i) decreasing urothelial stretch-induced ATP release; ii) dampening sensitised afferent nerve firing rates; and iii) reducing the contractile performance of detrusor smooth muscle.
- After the course, attendees will have the latest clinical and scientific information on the use of PDE5 inhibitors and sGC activators in treating LUTS. The information could be applied to attendees’ research programs or patient management strategies.
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