dc.creator | MONICA, F. Z. T. | |
dc.creator | BRICOLA, A. A. O. | |
dc.creator | BAU, F. R. | |
dc.creator | FREITAS, L. L. Lopes | |
dc.creator | TEIXEIRA, S. A. | |
dc.creator | MUSCARA, M. N. | |
dc.creator | ABDALLA, F. M. F. | |
dc.creator | PORTO, C. S. | |
dc.creator | NUCCI, G. De | |
dc.creator | ZANESCO, A. | |
dc.creator | ANTUNES, E. | |
dc.date.accessioned | 2012-10-20T03:20:48Z | |
dc.date.accessioned | 2018-07-04T15:35:31Z | |
dc.date.available | 2012-10-20T03:20:48Z | |
dc.date.available | 2018-07-04T15:35:31Z | |
dc.date.created | 2012-10-20T03:20:48Z | |
dc.date.issued | 2008 | |
dc.identifier | BRITISH JOURNAL OF PHARMACOLOGY, v.153, n.8, p.1659-1668, 2008 | |
dc.identifier | 0007-1188 | |
dc.identifier | http://producao.usp.br/handle/BDPI/28221 | |
dc.identifier | 10.1038/bjp.2008.39 | |
dc.identifier | http://dx.doi.org/10.1038/bjp.2008.39 | |
dc.identifier.uri | http://repositorioslatinoamericanos.uchile.cl/handle/2250/1624865 | |
dc.description.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. | |
dc.language | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.relation | British Journal of Pharmacology | |
dc.rights | Copyright NATURE PUBLISHING GROUP | |
dc.rights | restrictedAccess | |
dc.subject | detrusor smooth muscle | |
dc.subject | overactive bladder | |
dc.subject | inositol triphosphate | |
dc.subject | muscarinic receptors | |
dc.subject | trigone | |
dc.subject | beta-adrenoceptors | |
dc.title | Long-term nitric oxide deficiency causes muscarinic supersensitivity and reduces beta(3)-adrenoceptor-mediated relaxation, causing rat detrusor overactivity | |
dc.type | Artículos de revistas | |