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Soluble Guanylate Cyclase Activators to Treat Benign Prostatic Hyperplasia and associated LUTS

Kanai, A. J. ; Andersson, K. E. LU orcid ; Birder, L. A. and Fry, C. H. LU (2023) In Continence 6.
Abstract

This review summarises the presentations during a workshop session entitled “The Use of Soluble Guanylate Cyclase Activators to Treat Benign Prostatic Hyperplasia, Obstruction and Fibrosis – Mechanistic Concepts and Clinical Implications” at the International Continence Society (ICS) 2021 Melbourne Virtual meeting. Benign prostatic hyperplasia (BPH) is a highly prevalent condition that can result in bladder outflow obstruction (BOO) and development of lower urinary tract symptoms (LUTS), and by 80 years of age is present in about 75% of men. Current pharmacological therapies include α-adrenoceptor antagonists, 5α-reductase inhibitors, and the phosphodiesterase type 5 (PDE5) inhibitor, tadalafil. The efficacy of tadalafil suggests a role... (More)

This review summarises the presentations during a workshop session entitled “The Use of Soluble Guanylate Cyclase Activators to Treat Benign Prostatic Hyperplasia, Obstruction and Fibrosis – Mechanistic Concepts and Clinical Implications” at the International Continence Society (ICS) 2021 Melbourne Virtual meeting. Benign prostatic hyperplasia (BPH) is a highly prevalent condition that can result in bladder outflow obstruction (BOO) and development of lower urinary tract symptoms (LUTS), and by 80 years of age is present in about 75% of men. Current pharmacological therapies include α-adrenoceptor antagonists, 5α-reductase inhibitors, and the phosphodiesterase type 5 (PDE5) inhibitor, tadalafil. The efficacy of tadalafil suggests a role for nitric oxide (NO•) through activation of soluble guanylate cyclase (sGC) and production of cyclic guanosine 3’5’-monophosphate (cGMP), a cyclic nucleotide that relaxes smooth muscle, reduces neurotransmitter release and also acts as an antifibrotic agent. Patient refractoriness to tadalafil may be, for example, due to sGC inactivation due to oxidative stress. The workshop discussed the superiority of cinaciguat, an sGC activator that functions even when the enzyme is oxidised, over PDE5 inhibitors, and potentially its use in combination with agents that reduce formation of reactive oxygen species.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
8-aminoguanine (8AG), Benign prostatic hyperplasia (BPH), Bladder outlet obstruction (BOO), Lower urinary tract symptoms (LUTS), Purine nucleotide phosphorylase (PNPase), Soluble guanylate cyclase (sGC) activators
in
Continence
volume
6
article number
100699
publisher
Elsevier
external identifiers
  • pmid:37389026
  • scopus:85173920151
ISSN
2772-9737
DOI
10.1016/j.cont.2023.100699
language
English
LU publication?
yes
id
812e700c-571d-4a73-b4c2-df6d688cdbb2
date added to LUP
2023-12-11 14:51:13
date last changed
2024-04-24 09:09:38
@article{812e700c-571d-4a73-b4c2-df6d688cdbb2,
  abstract     = {{<p>This review summarises the presentations during a workshop session entitled “The Use of Soluble Guanylate Cyclase Activators to Treat Benign Prostatic Hyperplasia, Obstruction and Fibrosis – Mechanistic Concepts and Clinical Implications” at the International Continence Society (ICS) 2021 Melbourne Virtual meeting. Benign prostatic hyperplasia (BPH) is a highly prevalent condition that can result in bladder outflow obstruction (BOO) and development of lower urinary tract symptoms (LUTS), and by 80 years of age is present in about 75% of men. Current pharmacological therapies include α-adrenoceptor antagonists, 5α-reductase inhibitors, and the phosphodiesterase type 5 (PDE5) inhibitor, tadalafil. The efficacy of tadalafil suggests a role for nitric oxide (NO•) through activation of soluble guanylate cyclase (sGC) and production of cyclic guanosine 3’5’-monophosphate (cGMP), a cyclic nucleotide that relaxes smooth muscle, reduces neurotransmitter release and also acts as an antifibrotic agent. Patient refractoriness to tadalafil may be, for example, due to sGC inactivation due to oxidative stress. The workshop discussed the superiority of cinaciguat, an sGC activator that functions even when the enzyme is oxidised, over PDE5 inhibitors, and potentially its use in combination with agents that reduce formation of reactive oxygen species.</p>}},
  author       = {{Kanai, A. J. and Andersson, K. E. and Birder, L. A. and Fry, C. H.}},
  issn         = {{2772-9737}},
  keywords     = {{8-aminoguanine (8AG); Benign prostatic hyperplasia (BPH); Bladder outlet obstruction (BOO); Lower urinary tract symptoms (LUTS); Purine nucleotide phosphorylase (PNPase); Soluble guanylate cyclase (sGC) activators}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Continence}},
  title        = {{Soluble Guanylate Cyclase Activators to Treat Benign Prostatic Hyperplasia and associated LUTS}},
  url          = {{http://dx.doi.org/10.1016/j.cont.2023.100699}},
  doi          = {{10.1016/j.cont.2023.100699}},
  volume       = {{6}},
  year         = {{2023}},
}