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Pharmacological modulation of the micturition pattern in normal and cyclophosphamide pre-treated conscious rats.

Journal article
Authors Michael Andersson
Patrik Aronsson
Daniel Giglio
A Wilhelmson
P Jeřábek
Gunnar Tobin
Published in Autonomic neuroscience : basic & clinical
Volume 159
Issue 1-2
Pages 77-83
ISSN 1872-7484
Publication year 2011
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 77-83
Language en
Links dx.doi.org/10.1016/j.autneu.2010.08...
Subject categories Pharmacology

Abstract

In the current study, we wanted to assess the influence of muscarinic receptors, nitric oxide and purinoceptors on the micturition pattern of conscious normal and cyclophosphamide (CYP) pre-treated rats. The micturition parameters were assessed using a metabolic cage. Rats were pre-treated with either saline or CYP, to induce cystitis, followed by treatment with either the muscarinic M1/M3/M5 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), the nitric oxide synthase blocker N(ω)-nitro-L-arginine methyl (L-NAME), the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) or a combination of 4-DAMP with PPADS or L-NAME. Voiding volumes per micturition event were significantly lower in CYP pre-treated than in saline pre-treated rats. Neither 4-DAMP nor L-NAME had any effect in the normal rats, whereas PPADS reduced the micturition volume per event. In CYP pre-treated rats, 4-DAMP and L-NAME significantly increased voiding volumes per event and micturition frequency, respectively. 4-DAMP dose-dependently reduced the differences in micturition activity between saline and CYP pre-treated rats. We show that cystitis changes the urodynamics in conscious rats and that this change seems to depend on the production of NO and on altered muscarinic receptor effects. The altered muscarinic receptor responses are likely to per se involve NO-mediated mechanisms.

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