{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T04:19:57Z","timestamp":1697343597000},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,9,18]],"date-time":"2012-09-18T00:00:00Z","timestamp":1347926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>New findings<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p><jats:p>Nitric oxide is known to relax the internal anal sphincter, but its effect on the external anal sphincter is unknown. A topical NO donor (nitroglycerin) is used as an alternative to internal sphincterotomy in the treatment of chronic anal fissures. We investigated the potential effects of nitric oxide on the external anal sphincter and its motor nerve supply.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p><jats:p>This study is the first to investigate the effect of NO on the external anal sphincter and shows that its contraction is not modulated by NO, by pudendal nitrergic fibres or by NO diffusion from neighbouring nitrergic plexuses of the anal canal.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>Nitric oxide is known to relax the internal anal sphincter, but its effect on the external anal sphincter (EAS) is unknown. The aim of this study was to investigate whether there is a nitrergic nerve plexus that modulates the EAS, similar to that found in oesophageal striated muscle. An <jats:italic>in vitro<\/jats:italic> ring preparation of rat anal canal was used to evaluate the effects of the nitric oxide synthase inhibitor <jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine (<jats:sc>l<\/jats:sc>\u2010NNA) and the NO donor sodium nitroprusside (SNP) on the EAS in conditions of neuromuscular blockade and the effect of SNP on nerve\u2010evoked contractions. Immunohistological experiments were conducted to determine whether the neuronal isoform of nitric oxide synthase (nNOS) is present in the EAS. During direct muscle stimulation neither <jats:sc>l<\/jats:sc>\u2010NNA (<jats:italic>P<\/jats:italic>= 0.32) nor SNP (<jats:italic>P<\/jats:italic>= 0.19) significantly changed the EF<jats:sub>50<\/jats:sub>, which is the frequency at which 50% of maximal contraction is reached, compared with a time\u2010dependent control. Nerve\u2010evoked contractions were also not altered by addition of SNP to the tissue bath. Immunohistohistological experiments clearly showed co\u2010localization of nNOS\u2010positive nerve fibres at motor endplates of the oesophagus but not in the EAS. The internal anal sphincter was richly innervated by nitrergic fibres, but these did not extend into the EAS. In conclusion, there are no nitrergic motor fibres innervating the EAS, neurotransmission at the motor endplates is not affected by NO, and NO does not affect muscle force directly in conditions of neuromuscular blockade. There is, therefore, no evidence that EAS contraction is directly modulated by NO or by pudendal nitrergic fibres or diffusion from neighbouring nitrergic plexuses of the anal canal.<\/jats:p>","DOI":"10.1113\/expphysiol.2012.067413","type":"journal-article","created":{"date-parts":[[2012,8,8]],"date-time":"2012-08-08T01:24:06Z","timestamp":1344389046000},"page":"397-404","source":"Crossref","is-referenced-by-count":0,"title":["Is there a nitrergic modulation of the rat external anal sphincter?"],"prefix":"10.1113","volume":"98","author":[{"given":"J.","family":"Evers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Buffini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Craven","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. 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