{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T07:39:47Z","timestamp":1767857987643,"version":"3.49.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":3999,"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":[[1998,3]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>There is conflicting evidence in the literature concerning the role of cyclic GMP in the regulation of myometrial contractility and the importance of hormonal status on the uterine response to cyclic GMP\u2010elevating agents. The objective of the present study was to investigate further the importance of cyclic GMP in the control of uterine contractility, by monitoring the effects of cyclic GMP\u2010elevating agents on spontaneous contractions and cyclic GMP levels in myometrial strips from pregnant rats and from ovariectomized rats under the influence of oestrogen and\/or progesterone.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sodium nitroprusside (SNP) 5\u2003m<jats:sc>M<\/jats:sc>, atrial natriuretic peptide (ANP) 100\u2003n<jats:sc>M<\/jats:sc>, <jats:sc>L<\/jats:sc>\u2010arginine 1\u2003m<jats:sc>M<\/jats:sc> and 8\u2010bromo\u2010cyclic GMP 100\u2003m<jats:sc>M<\/jats:sc> had no relaxant effect on the spontaneous contractions of myometria from pregnant rats or from ovariectomized rats under the influence of oestrogen or progesterone.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Tissue levels of cyclic GMP were significantly elevated by SNP in all treatment groups, including pregnant animals. For example, in ovariectomized, progesterone\u2010treated rats, SNP raised cyclic GMP levels approximately 8 fold from a basal level of 2.9\u00b10.4\u2003pmol\u2003mg<jats:sup>\u22121<\/jats:sup> protein to 24.8\u00b14.0\u2003pmol\u2003mg<jats:sup>\u22121<\/jats:sup> protein. ANP increased cyclic GMP levels approximately 2 fold in all treatment groups, except in the pregnant animals. <jats:sc>L<\/jats:sc>\u2010Arginine elevated cyclic GMP significantly only in ovariectomized, vehicle\u2010treated myometria.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The activity of cyclic GMP\u2010dependent protein kinase (PKG) was significantly increased (3 fold) in myometria exposed to SNP (5\u2003m<jats:sc>M<\/jats:sc>). Thus, the inability of SNP to relax uterine preparations was not due to a failure of SNP\u2010elevated cyclic GMP to activate PKG.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The more potent NO donor, S\u2010nitroso\u2010N\u2010acetylpenicillamine (SNAP), at a concentration of 100\u2003\u03bc<jats:sc>M<\/jats:sc> was able to inhibit spontaneous contractions significantly in myometrial preparations from both non\u2010ovariectomized and ovariectomized rats treated with oestrogen or progesterone.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Tissue levels of cyclic GMP were markedly increased by SNAP at concentrations of 10, 30 and 100\u2003\u03bc<jats:sc>M<\/jats:sc>. At 100\u2003\u03bc<jats:sc>M<\/jats:sc>, cyclic GMP levels increased from 1.9\u00b10.2\u2003pmol\u2003mg<jats:sup>\u22121<\/jats:sup> protein to 74.0\u00b118.0\u2003pmol\u2003mg<jats:sup>\u22121<\/jats:sup> protein. However, complete or partial blockade of SNAP\u2010induced increases in cyclic GMP levels by the soluble guanylyl cyclase inhibitor, ODQ (25\u2003\u03bc<jats:sc>M<\/jats:sc>), had no effect on the relaxant response to SNAP. Thus, the relaxant effect of SNAP in this tissue appears to be mediated via a mechanism independent of cyclic GMP.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Taken as a whole, the results of the present study indicate that cyclic GMP does not play an important role in the control of contractility in the rat uterus.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>123<\/jats:bold>, 959\u2013967; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701678\">10.1038\/sj.bjp.0701678<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701678","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:24:26Z","timestamp":1106940266000},"page":"959-967","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Evidence that spontaneous contractile activity in the rat myometrium is not inhibited by NO\u2010mediated increases in tissue levels of cyclic GMP"],"prefix":"10.1111","volume":"123","author":[{"given":"James K.","family":"Hennan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Diamond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/368850a0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(95)90500-6"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"9589","DOI":"10.1016\/S0021-9258(19)50131-4","article-title":"A phenylalanine in peptide substrates provides for selectivity between cGMP\u2010 and cAMP\u2010dependent protein kinases","volume":"267","author":"Colbran J.L.","year":"1992","journal-title":"J. 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