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In cystitis, urothelial muscarinic NO-linked effects hamper contractility. Therefore we wondered if a blockade of this axis also affects the induction of cystitis in the rat. Rats were pretreated with saline, the muscarinic receptor antagonist 4-DAMP (1\u2009mg\/kg ip), or the NOS inhibitor L-NAME (30\u2009mg\/kg ip) for five days. 60\u2009h before the experiments the rats were treated with saline or CYP. Methacholine-, ATP-, and adenosine-evoked responses were smaller in preparations from CYP-treated rats than from saline-treated ones. Pretreatment with 4-DAMP did not change this relation, while pretreatment with L-NAME normalized the responses in the CYP-treated animals. The functional results were strengthened by the morphological observations; 4-DAMP pretreatment did not affect the parameters studied, namely, expression of muscarinic M5 receptors, P1A1 purinoceptors, mast cell distribution, or bladder wall enlargement. However, pretreatment with L-NAME attenuated the differences. Thus, the current study provides new insights into the complex mechanisms behind CYP-induced cystitis. The NO effects coupled to urothelial muscarinic receptors have a minor role in the development of cystitis. Inhibition of NOS may prevent the progression of cystitis.<\/jats:p>","DOI":"10.1155\/2014\/359179","type":"journal-article","created":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T21:05:36Z","timestamp":1401656736000},"page":"1-12","source":"Crossref","is-referenced-by-count":14,"title":["Inhibition of Nitric Oxide Synthase Prevents Muscarinic and Purinergic Functional Changes and Development of Cyclophosphamide-Induced Cystitis in the Rat"],"prefix":"10.1155","volume":"2014","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9970-817X","authenticated-orcid":true,"given":"Patrik","family":"Aronsson","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, P.O. 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