{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:13:52Z","timestamp":1791346432891,"version":"4.3.1"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":303,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose:<\/jats:title>\n                    <jats:p>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\u2010term nitric oxide (NO) deficiency on muscarinic receptor and \u03b2\u2010adrenoceptor modulation leading to overactivity of rat detrusor muscle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach:<\/jats:title>\n                    <jats:p>\n                      Male Wistar rats received\n                      <jats:italic>N<\/jats:italic>\n                      <jats:sup>\u03c9<\/jats:sup>\n                      \u2010nitro\u2010\n                      <jats:sc>L<\/jats:sc>\n                      \u2010arginine methyl ester (\n                      <jats:sc>L<\/jats:sc>\n                      \u2010NAME) in drinking water for 7\u201330 days. Functional responses to muscarinic and \u03b2\u2010adrenoceptor agonists were measured in detrusor smooth muscle (DSM) strips in Krebs\u2013Henseleit solution. Measurements of [\n                      <jats:sup>3<\/jats:sup>\n                      H]inositol phosphate, NO synthase (NOS) activity, [\n                      <jats:sup>3<\/jats:sup>\n                      H]quinuclidinyl benzilate ([\n                      <jats:sup>3<\/jats:sup>\n                      H]QNB) binding and bladder morphology were also performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results:<\/jats:title>\n                    <jats:p>\n                      Long\u2010term\n                      <jats:sc>L<\/jats:sc>\n                      \u2010NAME treatment significantly increased carbachol\u2010induced DSM contractile responses after 15 and 30 days; relaxing responses to the \u03b2\n                      <jats:sub>3<\/jats:sub>\n                      \u2010adrenoceptor agonist BRL 37\u2010344 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\n                      <jats:sc>L<\/jats:sc>\n                      \u2010NAME treatment. Carbachol increased sixfold the [\n                      <jats:sup>3<\/jats:sup>\n                      H]inositol phosphate in bladder tissue from rats treated with\n                      <jats:sc>L<\/jats:sc>\n                      \u2010NAME. [\n                      <jats:sup>3<\/jats:sup>\n                      H]QNB was bound with an apparent\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sub>D<\/jats:sub>\n                      twofold higher in bladder membranes after\n                      <jats:sc>L<\/jats:sc>\n                      \u2010NAME treatment compared with that in control. No morphological alterations in DSM were found.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications:<\/jats:title>\n                    <jats:p>\n                      Long\u2010term NO deficiency increased rat DSM contractile responses to a muscarinic agonist, accompanied by significantly enhanced\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sub>D<\/jats:sub>\n                      values for muscarinic receptors and [\n                      <jats:sup>3<\/jats:sup>\n                      H]inositol phosphate accumulation in bladder. This supersensitivity for muscarinic agonists along with reductions of \u03b2\n                      <jats:sub>3<\/jats:sub>\n                      \u2010adrenoceptor\u2010mediated relaxations indicated that overactive DSM resulted from chronic NO deficiency.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:italic>British Journal of Pharmacology<\/jats:italic>\n                      (2008)\n                      <jats:bold>153<\/jats:bold>\n                      , 1659\u20131668; doi:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.39\">10.1038\/bjp.2008.39<\/jats:ext-link>\n                      ; published online 25 February 2008\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/bjp.2008.39","type":"journal-article","created":{"date-parts":[[2008,2,25]],"date-time":"2008-02-25T06:17:12Z","timestamp":1203920232000},"page":"1659-1668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Long\u2010term nitric oxide deficiency causes muscarinic supersensitivity and reduces \u03b2\n                    <sub>3<\/sub>\n                    \u2010adrenoceptor\u2010mediated relaxation, causing rat detrusor overactivity"],"prefix":"10.1111","volume":"153","author":[{"given":"F Z T","family":"M\u00f3nica","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A A O","family":"Bricola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F R","family":"B\u00e1u","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L L 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