{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T22:26:06Z","timestamp":1775082366373,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":4385,"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":[[1997,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The flavoprotein binder diphenyleneiodonium (DPI) is a potent, irreversible inhibitor of nitric oxide synthase (NOS), but produces only a transient pressor response following systemic administration to animals, despite evidence of persistent NOS inhibition. To characterize further the effects of DPI on vascular tone, isometric tension was recorded from rat isolated aortic rings mounted between steel wires in an organ bath.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The NOS inhibitor N<jats:sup>G<\/jats:sup>\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine methyl ester (<jats:sc>l<\/jats:sc>\u2010NAME, 1 m<jats:sc>m<\/jats:sc>) initiated an additional contraction of prostaglandin F<jats:sub>2\u03b1<\/jats:sub>\u2010preconstricted rings with endothelium which was sustained throughout the period of <jats:sc>l<\/jats:sc>\u2010NAME exposure (+234\u00b139% at 15 min). In contrast, addition of DPI (5 \u03bc<jats:sc>m<\/jats:sc>) to rings with endothelium produced a transient initial contraction (+111\u00b127% at 2 min) followed by a more sustained relaxation (\u221227\u00b119% at 15 min, <jats:italic>P<\/jats:italic>&lt;0.001 vs <jats:sc>l<\/jats:sc>\u2010NAME).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The contraction to DPI was also observed in rings without endothelium, was abolished by <jats:sc>l<\/jats:sc>\u2010NAME pretreatment, and was unaffected by the \u03b1\u2010adrenoreceptor inhibitor prazosin. Relaxation in response to DPI was not inhibited by endothelium removal or by pretreatment with either <jats:sc>l<\/jats:sc>\u2010NAME or with the ATP\u2010sensitive potassium channel blocker glibenclamide.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The endothelium\u2010independent relaxation to DPI was inhibited at 23\u00b0C and its time course was delayed by pretreatment with the guanylate cyclase inhibitor methylene blue.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Thus, in addition to a transient initial contraction due to NOS inhibition, DPI produces an endothelium\u2010independent, temperature\u2010dependent relaxation which appears in part due to activation of guanylate cyclase. This relaxant effect of DPI may explain the transient nature of its pressor effect <jats:italic>in vivo<\/jats:italic> despite sustained NOS inhibition.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1997) <jats:bold>120<\/jats:bold>, 857\u2013864; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701014\">10.1038\/sj.bjp.0701014<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701014","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T16:10:42Z","timestamp":1156522242000},"page":"857-864","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Endothelium\u2010independent relaxation of aortic rings by the nitric oxide synthase inhibitor diphenyleneiodonium"],"prefix":"10.1111","volume":"120","author":[{"given":"Jeffrey M","family":"Dodd\u2010o","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard S","family":"Silverman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward G","family":"Lakatta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy C","family":"Ziegelstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)92517-5"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.1.71"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1887"},{"key":"e_1_2_6_5_1","first-page":"A101","article-title":"The nitric oxide synthase inhibitor diphenyleneiodonium relaxes vascular smooth muscle and decreases cytosolic pH","volume":"27","author":"Dodd\u2010O J.M.","year":"1995","journal-title":"J. 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