{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:04:38Z","timestamp":1787065478656,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:00:00Z","timestamp":1491868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK067223"],"award-info":[{"award-number":["R01DK067223"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To investigate detrusor function and\n                      <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\n                      activation as a possible target for detrusor overactivity in an experimental model lacking a key denitrosylation enzyme, S\u2010nitrosoglutathione reductase (\n                      <jats:styled-content style=\"fixed-case\">GSNOR<\/jats:styled-content>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">GSNOR<\/jats:styled-content>\n                      \u2010deficient (\n                      <jats:styled-content style=\"fixed-case\">GSNOR<\/jats:styled-content>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) (\n                      <jats:italic>n<\/jats:italic>\n                      = 30) and wild\u2010type (\n                      <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\n                      ) mice (\n                      <jats:italic>n<\/jats:italic>\n                      = 26) were treated for 7 days with the\n                      <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\n                      activator, colforsin (1 mg\/kg), or vehicle intraperitoneally. Cystometric studies or molecular analyses of bladder specimens were performed. Bladder function indices and expression levels of proteins that regulate detrusor relaxation (nitric oxide synthase pathway) or contraction (RhoA\/Rho\u2010kinase pathway) and oxidative stress were assessed. For statistical analysis the Student's\n                      <jats:italic>t<\/jats:italic>\n                      \u2010test and one\u2010way analysis of variance were used.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">GSNOR<\/jats:styled-content>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice had significantly higher (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05) voiding and non\u2010voiding contraction frequencies compared to\n                      <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\n                      mice (Cohen's effect size values\n                      <jats:italic>d<\/jats:italic>\n                      = 1.82 and 2.52, respectively). Colforsin normalised these abnormalities (Cohen's effect size values\n                      <jats:italic>d<\/jats:italic>\n                      = 1.85 and 1.28, respectively). Western blot analyses showed an up\u2010regulation of the RhoA\/Rho\u2010kinase pathway reflected by significantly higher (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05) phosphorylated myosin phosphatase target subunit 1 (P\u2010MYPT\u20101) expression in\n                      <jats:styled-content style=\"fixed-case\">GSNOR<\/jats:styled-content>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mouse bladders, which was reversed by colforsin treatment. There was a higher level (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05) of gp91\n                      <jats:sup>\n                        <jats:italic>phox<\/jats:italic>\n                      <\/jats:sup>\n                      expression in the bladders of\n                      <jats:styled-content style=\"fixed-case\">GSNOR<\/jats:styled-content>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice without significant change after colforsin treatment. Neuronal and endothelial nitric oxide synthase phosphorylation on Ser\u20101412 and Ser\u20101177, respectively, did not differ between\n                      <jats:styled-content style=\"fixed-case\">GSNOR<\/jats:styled-content>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and\n                      <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\n                      mouse bladders irrespective of colforsin treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Impaired denitrosylation is associated with detrusor overactivity, which is linked with upregulated RhoA\/Rho\u2010kinase signalling. Colforsin reverses physiological and molecular abnormalities. This study describes a novel model of detrusor overactivity and suggests a possible basis for its treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.13847","type":"journal-article","created":{"date-parts":[[2017,3,17]],"date-time":"2017-03-17T00:12:47Z","timestamp":1489709567000},"page":"143-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<scp>cAMP<\/scp>\n                    \u2010dependent regulation of RhoA\/Rho\u2010kinase attenuates detrusor overactivity in a novel mouse experimental model"],"prefix":"10.1111","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1683-0079","authenticated-orcid":false,"given":"William","family":"Akakpo","sequence":"first","affiliation":[{"name":"The James Buchanan Brady Urological Institute and Department of Urology The Johns Hopkins School of Medicine Baltimore MD 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