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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.