Hiding in Plain Sight: Nebivolol Exhibits Compelling Tocolytic Properties
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Authors
Barnett, Scott D.
Buxton, Iain L. O.
Issue Date
2018
Type
Article
Language
Keywords
GSNO , GSNOR GSNO reductase , ADH5 nebivolol , nitric oxide , pregnancy , preterm labour , smooth muscle , S?Nitrosoglutathione
Alternative Title
Abstract
Preterm birth before 37 weeks of completed gestation results in numerous health consequences for the foetus. Preterm labour leads to preterm birth in over 50% of cases, and no FDA-approved treatment can prevent labour or help a foetus remain in the womb until term. Examination of nitric oxide mediated relaxation signaling in the uterine smooth muscle reveals a role for protein S-nitrosation. The recent discovery of upregulated S-nitrosoglutathione reductase (GSNOR) in spontaneously preterm labouring women has emphasized the need to explore the function of S-nitrosation regulation in the maintenance of uterine quiescence. Here we have examined the ability of nebivolol to relax uterine smooth muscle and tested recent claims that nebivolol is a GSNOR inhibitor. In uterine smooth muscle strips from both mouse and human, nebivolol relaxes oxytocin-induced contractions in a dose dependent manner. Our data indicates that nebivolol has no effect on GSNOR activity, nor does nebivolol inhibit thioredoxin reductase, two of the major protein denitrosylases. The ability of nebivolol to relax uterine smooth muscle is likely the combined effects of increased nitric oxide synthase activity and beta 3-adregnegic stimulation.
Description
Citation
Barnett, S. D., & Buxton, I. L. O. (2018). Hiding in Plain Sight: Nebivolol Exhibits Compelling Tocolytic Properties. Journal of Cellular and Molecular Medicine, 22(12), 6391�"6395. doi:10.1111/jcmm.13883
Publisher
License
Creative Commons Attribution 4.0 International
Journal
Volume
Issue
PubMed ID
ISSN
1582-4934