Abstract
Functional studies have shown altered cholinergic mechanisms in the inflamed bladder,
which partly depend on muscarinic receptor-induced release of nitric oxide (NO). The
current study aimed to characterize which muscarinic receptor subtypes that are involved
in the regulation of the nitrergic effects in the bladder cholinergic response during
cystitis. For this purpose, in vitro examinations of carbachol-evoked contractions of inflamed and normal bladder preparations
were performed. The effects of antagonists with different selectivity for the receptor
subtypes were assessed on intact and urothelium-denuded bladder preparations. In preparations
from cyclophosphamide (CYP; in order to induce cystitis) pre-treated rats, the response
to carbachol was about 75% of that of normal preparations. Removal of the urothelium
or administration of a nitric oxide synthase inhibitor re-established the responses
in the inflamed preparations. Administration of 4-diphenylacetoxy-N-methylpiperidine
(4-DAMP) inhibited the carbachol-induced contractile responses of preparations from
CYP pre-treated rats less potently than controls. Pirenzepine and p-fluoro-hexahydro-sila-diphenidol
(pFHHSiD) affected the carbachol-induced contractile responses to similar extents
in preparations of CYP pre-treated and control rats. However, the Schild slopes for
the three antagonists were all significantly different from unity in the preparations
from CYP pre-treated rats. Again, l-NNA or removal of the urothelium eliminated any difference compared to normal preparations.
This study confirms that muscarinic receptor stimulation in the inflamed rat urinary
bladder induces urothelial release of NO, which counteracts detrusor contraction.
Keywords
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Article info
Publication history
Published online: July 12, 2012
Accepted:
June 18,
2012
Received in revised form:
June 13,
2012
Received:
November 30,
2011
Identification
Copyright
© 2012 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
