Nitric oxide signaling pathways in the normal and pathological bladder: Do they provide new pharmacological pathways?—ICI-RS 2023

Basu Chakrabarty, Michael Winder, Anthony Kanai, Hikaru Hashitani, Marcus Drake, Paul Abrams, Chris Fry*

*Corresponding author for this work

Research output: Contribution to journalReview article (Academic Journal)peer-review

1 Citation (Scopus)
58 Downloads (Pure)

Abstract

Aims
The nitric oxide (NO•)/soluble guanylate cyclase/cyclic-GMP (cGMP) signaling pathway is ubiquitous and regulates several functions in physiological systems as diverse as the vascular, nervous, and renal systems. However, its roles in determining normal and abnormal lower urinary tract functions are unclear. The aim was to identify potential therapeutic targets associated with this pathway to manage lower urinary tract functional disorders.

Methods
This review summarizes a workshop held under the auspices of ICI-RS with a view to address these questions.

Results
Four areas were addressed: NO• signaling to regulate neurotransmitter release to detrusor smooth muscle; its potential dual roles in alleviating and exacerbating inflammatory pathways; its ability to act as an antifibrotic mediator; and the control by nitrergic nerves of lower urinary tract vascular dynamics and the contractile performance of muscular regions of the bladder wall. Central to much of the discussion was the role of the NO• receptor, soluble guanylate cyclase (sGC) in regulating the generation of the enzyme product, the second messenger cGMP. The redox state of sGC is crucial in determining its enzymic activity and the role of a class of novel agents, sGC activators, to optimize activity and to potentially alleviate the consequences of lower urinary tract disorders was highlighted. In addition, the consequences of a functional relationship between nitrergic and sympathetic nerves to regulate vascular dynamics was discussed.

Conclusions
Several potential NO•-dependent drug targets in the lower urinary tract were identified that provide the basis for future research and translation to clinical trials.
Original languageEnglish
JournalNeurourology and Urodynamics
Early online date30 Oct 2023
DOIs
Publication statusE-pub ahead of print - 30 Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.

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