Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/946
Type: Artigo de periódico
Title: Long-term nitric oxide deficiency causes muscarinic supersensitivity and reduces beta(3)-adrenoceptor-mediated relaxation, causing rat detrusor overactivity
Author: MONICA, F. Z. T.
BRICOLA, A. A. O.
BAU, F. R.
FREITAS, L. L. Lopes
TEIXEIRA, S. A.
MUSCARA, M. N.
ABDALLA, F. M. F.
PORTO, C. S.
NUCCI, G. De
ZANESCO, A.
ANTUNES, E.
Abstract: Background and purpose: Overactive bladder is a complex and widely prevalent condition, but little is known about its physiopathology. We have carried out morphological, biochemical and functional assays to investigate the effects of long-term nitric oxide (NO) deficiency on muscarinic receptor and beta-adrenoceptor modulation leading to overactivity of rat detrusor muscle. Experimental approach: Male Wistar rats received No-nitro-L-arginine methyl ester (L-NAME) in drinking water for 7-30 days. Functional responses to muscarinic and b-adrenoceptor agonists were measured in detrusor smooth muscle (DSM) strips in Krebs-Henseleit solution. Measurements of [H-3] inositol phosphate, NO synthase (NOS) activity, [H-3] quinuclidinyl benzilate ([H-3]QNB) binding and bladder morphology were also performed. Key results: Long-term L-NAME treatment significantly increased carbachol-induced DSM contractile responses after 15 and 30 days; relaxing responses to the beta(3)-adrenoceptor agonist BRL 37-344 were significantly reduced at 30 days. Constitutive NOS activity in bladder was reduced by 86% after 7 days and maintained up to 30 days of L-NAME treatment. Carbachol increased sixfold the [H-3] inositol phosphate in bladder tissue from rats treated with L-NAME. [H-3] QNB was bound with an apparent KD twofold higher in bladder membranes after L-NAME treatment compared with that in control. No morphological alterations in DSM were found. Conclusions and implications: Long-term NO deficiency increased rat DSM contractile responses to a muscarinic agonist, accompanied by significantly enhanced KD values for muscarinic receptors and [H-3] inositol phosphate accumulation in bladder. This supersensitivity for muscarinic agonists along with reductions of beta(3)-adrenoceptor-mediated relaxations indicated that overactive DSM resulted from chronic NO deficiency.
Subject: detrusor smooth muscle
overactive bladder
inositol triphosphate
muscarinic receptors
trigone
beta-adrenoceptors
Country: Inglaterra
Editor: NATURE PUBLISHING GROUP
Rights: fechado
Identifier DOI: 10.1038/bjp.2008.39
Address: http://dx.doi.org/10.1038/bjp.2008.39
http://apps.isiknowledge.com/InboundService.do?Func=Frame&product=WOS&action=retrieve&SrcApp=EndNote&UT=000254960200009&Init=Yes&SrcAuth=ResearchSoft&mode=FullRecord
Date Issue: 2008
Appears in Collections:FCM - Artigos e Outros Documentos

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