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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: Mónica, F Z T
Bricola, A A O
Báu, F R
Freitas, L L Lopes
Teixeira, S A
Muscará, M N
Abdalla, F M F
Porto, C S
De Nucci, G
Zanesco, A
Antunes, E
Abstract: 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. Male Wistar rats received N(omega)-nitro-L-arginine methyl ester (L-NAME) in drinking water for 7-30 days. Functional responses to muscarinic and beta-adrenoceptor agonists were measured in detrusor smooth muscle (DSM) strips in Krebs-Henseleit solution. Measurements of [(3)H]inositol phosphate, NO synthase (NOS) activity, [(3)H]quinuclidinyl benzilate ([(3)H]QNB) binding and bladder morphology were also performed. 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 [(3)H]inositol phosphate in bladder tissue from rats treated with L-NAME. [(3)H]QNB was bound with an apparent K(D) twofold higher in bladder membranes after L-NAME treatment compared with that in control. No morphological alterations in DSM were found. Long-term NO deficiency increased rat DSM contractile responses to a muscarinic agonist, accompanied by significantly enhanced K(D) values for muscarinic receptors and [(3)H]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: Adrenergic Beta-3 Receptor Agonists
Adrenergic Beta-agonists
Inositol Phosphates
Muscarinic Agonists
Muscle Contraction
Muscle, Smooth
Ng-nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Rats, Wistar
Receptors, Adrenergic, Beta-3
Receptors, Muscarinic
Urinary Bladder
Urinary Bladder, Overactive
Citation: British Journal Of Pharmacology. v. 153, n. 8, p. 1659-68, 2008-Apr.
Rights: fechado
Identifier DOI: 10.1038/bjp.2008.39
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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