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10.1155/2014/359179

http://scihub22266oqcxt.onion/10.1155/2014/359179
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suck abstract from ncbi


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pmid24982868
      Biomed+Res+Int 2014 ; 2014 (ä): 359179
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  • Inhibition of nitric oxide synthase prevents muscarinic and purinergic functional changes and development of cyclophosphamide-induced cystitis in the rat #MMPMID24982868
  • Aronsson P ; Vesela R ; Johnsson M ; Tayem Y ; Wsol V ; Winder M ; Tobin G
  • Biomed Res Int 2014[]; 2014 (ä): 359179 PMID24982868 show ga
  • Nitric oxide (NO) has pivotal roles in cyclophosphamide- (CYP-) induced cystitis during which mucosal nitric oxide synthase (NOS) and muscarinic M5 receptor expressions are upregulated. 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?mg/kg ip), or the NOS inhibitor L-NAME (30?mg/kg ip) for five days. 60?h 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.
  • |Adenosine Triphosphate/pharmacology [MESH]
  • |Adenosine/pharmacology [MESH]
  • |Animals [MESH]
  • |Cyclophosphamide [MESH]
  • |Cystitis/*drug therapy/pathology/*physiopathology [MESH]
  • |Enzyme Inhibitors/*pharmacology/*therapeutic use [MESH]
  • |Immunohistochemistry [MESH]
  • |In Vitro Techniques [MESH]
  • |Male [MESH]
  • |Mast Cells/drug effects/pathology [MESH]
  • |Methacholine Chloride/pharmacology [MESH]
  • |Muscle Contraction/drug effects [MESH]
  • |Nitric Oxide Synthase/*antagonists & inhibitors/metabolism [MESH]
  • |Rats, Sprague-Dawley [MESH]
  • |Receptors, Muscarinic/*metabolism [MESH]
  • |Receptors, Purinergic/*metabolism [MESH]


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