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Inhibition of Nitric Oxide Synthase Prevents Muscarinic and Purinergic Functional Changes and Development of Cyclophosphamide-Induced Cystitis in the Rat

Artikel i vetenskaplig tidskrift
Författare Patrik Aronsson
Renata Vesela
Martin Johnsson
Y. Tayem
V. Wsol
Michael Winder
Gunnar Tobin
Publicerad i Biomed research international
Sidor Article ID 359179
ISSN 2314-6133
Publiceringsår 2014
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor Article ID 359179
Språk en
Länkar dx.doi.org/10.1155/2014/359179
Ämneskategorier Medicinsk bioteknologi

Sammanfattning

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 (1mg/kg ip), or the NOS inhibitor L-NAME (30mg/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.

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