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Cholinergic nitric oxide release from the urinary bladder mucosa in cyclophosphamide-induced cystitis of the anaesthetized rat.

Journal article
Authors Michael Andersson
Gunnar Tobin
Daniel Giglio
Published in British journal of pharmacology
Volume 153
Issue 7
Pages 1438-44
ISSN 0007-1188
Publication year 2008
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 1438-44
Language en
Links dx.doi.org/10.1038/bjp.2008.6
Subject categories Pharmacology

Abstract

Background and purpose: Previous reports have suggested that nitric oxide (NO) may be released by cholinergic stimuli in the rat bladder in cyclophosphamide-induced cystitis, affecting bladder function. In the current study, we evaluated the effects of cyclophosphamide-induced cystitis on muscarinic whole bladder contractile responses in vivo, and further, if NO might be released from the mucosa by cholinergic stimuli.Experimental approach: Male rats were pre-treated either with cyclophosphamide (100 mg kg(-1); to induce cystitis) or saline (serving as controls). 60 h later, rats were anaesthetized and bladder pressure monitored.Key results: The muscarinic receptor agonist methacholine (MeCh; 0.5-5 mug kg(-1) i.v.) induced similar contractions (i.e. bladder pressure increases) in inflamed bladders as in controls, which were attenuated dose-dependently by the muscarinic M(1)/M(3)/M(5) antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; 0.1-1000 mug kg(-1) i.v.). In inflamed bladders, the cholinergic bladder contractions were enhanced after removing the mucosa, while cholinergic contractions were similar in intact and urothelium-denuded inflamed bladders in the presence of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 30 mg kg(-1) i.v.). L-NAME attenuated the antagonistic effect of 4-DAMP on MeCh-induced contractions in intact inflamed bladders. However L-NAME did not affect the antagonism by 4-DAMP of MeCh-induced contractions of urothelium-denuded bladders, under control conditions or with cyclophosphamide-induced cystitis.Conclusions and implications: In cyclophosphamide-induced 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(3)/M(5) receptors, presumably on urothelial cells, affecting bladder function.British Journal of Pharmacology (2008) 153, 1438-1444; doi:10.1038/bjp.2008.6; published online 4 February 2008.

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