{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:03:04Z","timestamp":1788343384362,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":303,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:p><jats:bold>Background and purpose:<\/jats:bold> Previous reports have suggested that nitric oxide (NO) may be released by cholinergic stimuli in the rat bladder in cyclophosphamide\u2010induced cystitis, affecting bladder function. In the current study, we evaluated the effects of cyclophosphamide\u2010induced cystitis on muscarinic whole bladder contractile responses <jats:italic>in vivo<\/jats:italic>, and further, if NO might be released from the mucosa by cholinergic stimuli.<\/jats:p><jats:p><jats:bold>Experimental approach:<\/jats:bold> Male rats were pre\u2010treated either with cyclophosphamide (100\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>; to induce cystitis) or saline (serving as controls). 60\u2003h later, rats were anaesthetized and bladder pressure monitored.<\/jats:p><jats:p><jats:bold>Key results:<\/jats:bold> The muscarinic receptor agonist methacholine (MeCh; 0.5\u20135\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup> i.v.) induced similar contractions (i.e. bladder pressure increases) in inflamed bladders as in controls, which were attenuated dose\u2010dependently by the muscarinic M<jats:sub>1<\/jats:sub>\/M<jats:sub>3<\/jats:sub>\/M<jats:sub>5<\/jats:sub> antagonist 4\u2010diphenylacetoxy\u2010<jats:italic>N<\/jats:italic>\u2010methylpiperidine (4\u2010DAMP; 0.1\u20131000\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup> i.v.). In inflamed bladders, the cholinergic bladder contractions were enhanced after removing the mucosa, while cholinergic contractions were similar in intact and urothelium\u2010denuded inflamed bladders in the presence of the NO synthase inhibitor <jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>\u2010nitro\u2010<jats:sc>L<\/jats:sc>\u2010arginine methyl ester (<jats:sc>L<\/jats:sc>\u2010NAME; 30\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> i.v.). <jats:sc>L<\/jats:sc>\u2010NAME attenuated the antagonistic effect of 4\u2010DAMP on MeCh\u2010induced contractions in intact inflamed bladders. However <jats:sc>L<\/jats:sc>\u2010NAME did not affect the antagonism by 4\u2010DAMP of MeCh\u2010induced contractions of urothelium\u2010denuded bladders, under control conditions or with cyclophosphamide\u2010induced cystitis.<\/jats:p><jats:p><jats:bold>Conclusions and implications:<\/jats:bold> In cyclophosphamide\u2010induced cystitis, the cholinergic function of the bladder is altered. In the inflamed bladder, NO seems to be released via cholinergic stimuli through mucosal muscarinic M<jats:sub>3<\/jats:sub>\/M<jats:sub>5<\/jats:sub> receptors, presumably on urothelial cells, affecting bladder function.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2008) <jats:bold>153<\/jats:bold>, 1438\u20131444; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.6\">10.1038\/bjp.2008.6<\/jats:ext-link>; published online 4 February 2008<\/jats:p>","DOI":"10.1038\/bjp.2008.6","type":"journal-article","created":{"date-parts":[[2008,2,4]],"date-time":"2008-02-04T11:21:34Z","timestamp":1202124094000},"page":"1438-1444","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Cholinergic nitric oxide release from the urinary bladder mucosa in cyclophosphamide\u2010induced cystitis of the anaesthetized 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