{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T09:48:37Z","timestamp":1695894517313},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":2711,"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":[[2001,9]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item>\n<jats:p>Recent studies indicate that nitroglycerin (NTG) can produce beneficial clinical effects in healing anal fissures through the relaxation of the internal anal sphincter. The <jats:italic>in vivo<\/jats:italic> relaxation effects of NTG on the anorectal smooth muscle have not been studied and it is not known whether this tissue may also exhibit pharmacological tolerance toward NTG.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>We have developed an <jats:italic>in vivo<\/jats:italic> procedure in the anaesthetized rat that permits continual monitoring of anorectal pressure after intravenous (i.v.) and intra\u2010rectal application of NTG. The relaxant effects of NTG were quantified <jats:italic>via<\/jats:italic> the area\u2010under\u2010the\u2010contraction\u2010waveforms vs time curve (AUEC).<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>AUEC decreased significantly after intra\u2010rectal bolus doses of NTG (5\u2003\u2013\u200325\u2003\u03bcg), in a dose\u2010 and time\u2010dependent manner. Sustained relaxation effects on anorectal pressure were also observed after continuous intra\u2010rectal infusions of NTG.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Two\u2010hours of i.v. NTG infusion led to a significant reduction in the mean arterial blood pressure (MAP) response toward a i.v. NTG (30\u2003\u03bcg) bolus challenge. In contrast, relaxation of the anorectal pressure toward the challenge dose was not altered after NTG infusion.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>In isolated tissues, cyclic GMP accumulation was significantly decreased after NTG pre\u2010incubation in the rat aorta but not in the rat anorectal smooth muscle and anal sphincter.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>These results indicate that the relaxation response toward NTG was not diminished in the anorectum under conditions that produced vascular tolerance. Thus, NTG causes significant and sustained <jats:italic>in vivo<\/jats:italic> relaxation of anorectal smooth muscle in the anaesthetized rat without evidence of tolerance development.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>134<\/jats:bold>, 418\u2013424; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704239\">10.1038\/sj.bjp.0704239<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704239","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T22:01:54Z","timestamp":1106949714000},"page":"418-424","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nitroglycerin\u2010induced relaxation of anorectal smooth muscle: evidence for apparent lack of tolerance development in the anaesthetized rat"],"prefix":"10.1111","volume":"134","author":[{"given":"Ellen Q","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Soda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ho\u2010Leung","family":"Fung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018917522072"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199609000-00013"},{"key":"e_1_2_7_4_1","first-page":"938","article-title":"Formation of reactive oxygen species by pentaerithrityltetranitrate and glyceryl trinitrate in vitro and development of nitrate tolerance","volume":"286","author":"DIKALOV S.","year":"1998","journal-title":"J. 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