{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T23:09:11Z","timestamp":1770332951315,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3042,"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":[[2000,10]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>In rat pulmonary artery pre\u2010contracted with phenylephrine, the mechanisms of relaxation to the nitric oxide (NO) donor, spermine NONOate, were investigated.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Responses to spermine NONOate were only partially blocked by the soluble guanylate cyclase inhibitor, ODQ (1<jats:italic>H<\/jats:italic>\u2010[1,2,4]Oxadiazolo\u2010[4,3,\u2010<jats:italic>a<\/jats:italic>]quinoxalin\u20101\u2010one) at concentrations up to 30\u2003\u03bc<jats:sc>M<\/jats:sc>. Ten \u03bc<jats:sc>M<\/jats:sc> ODQ gave maximal inhibition. Endothelium removal had no effect on the potency of spermine NONOate or its inhibition by ODQ.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The protein kinase G inhibitor, Rp\u20108\u2010Br\u2010cGMPS (100\u2003\u03bc<jats:sc>M<\/jats:sc>), caused minimal inhibition of spermine NONOate despite causing marked inhibition of glyceryl trinitrate and isosorbide dinitrate.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Spermine NONOate (100\u2003\u03bc<jats:sc>M<\/jats:sc>) caused a 35 fold increase in guanosine 3\u20325\u2032 cyclic monophosphate (cyclic GMP) above basal levels in pulmonary artery rings. ODQ (3\u2003\u03bc<jats:sc>M<\/jats:sc>) abolished this cyclic GMP production but did not inhibit corresponding relaxant responses. Similar results were seen with another NONOate (MAHMA NONOate; 10\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ODQ\u2010resistant relaxation to spermine NONOate (i.e. relaxation seen in the presence of 10\u2003\u03bc<jats:sc>M<\/jats:sc> ODQ) was inhibited by potassium (80\u2003m<jats:sc>M<\/jats:sc>), charybdotoxin (300\u2003n<jats:sc>M<\/jats:sc>), iberiotoxin (300\u2003n<jats:sc>M<\/jats:sc>), apamin (100\u2003n<jats:sc>M<\/jats:sc>), ouabain (1\u2003m<jats:sc>M<\/jats:sc>) or thapsigargin (100\u2003n<jats:sc>M<\/jats:sc>) but not by 4\u2010aminopyridine (3\u2003m<jats:sc>M<\/jats:sc>), glybenclamide (10\u2003\u03bc<jats:sc>M<\/jats:sc>) or diltiazem (10\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Potassium, charybdotoxin, ouabain and thapsigargin also inhibited ODQ\u2010resistant relaxation to FK409 ((\u00b1)\u2010<jats:italic>E<\/jats:italic>\u20104\u2010ethyl\u20102\u2010[<jats:italic>E<\/jats:italic>\u2010hydroxyimino]\u20105\u2010nitro\u20103\u2010hexenamide).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that, on rat pulmonary artery, spermine NONOate can produce cyclic GMP\u2010independent relaxation that involves, at least in part, activation of Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>\u2010ATPase, sarco\u2010endoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>\u2010ATPase and calcium\u2010activated potassium channels.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>131<\/jats:bold>, 673\u2013682; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703613\">10.1038\/sj.bjp.0703613<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703613","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:58:37Z","timestamp":1106945917000},"page":"673-682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Cyclic GMP\u2010independent relaxation of rat pulmonary artery by spermine NONOate, a diazeniumdiolate nitric oxide donor"],"prefix":"10.1111","volume":"131","author":[{"given":"Kerry L","family":"Homer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet C","family":"Wanstall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.16.7583"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.3.431"},{"key":"e_1_2_7_4_1","first-page":"48","article-title":"Novel guanylyl cyclase inhibitor potently inhibits cyclic GMP accumulation in endothelial cells and relaxation of bovine pulmonary artery","volume":"277","author":"BRUNNER F.","year":"1996","journal-title":"J. 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