{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T23:07:21Z","timestamp":1771024041184,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2981,"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":[[2000,12]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The 4\u2010amino analogue of tetrahydrobiopterin (4\u2010ABH<jats:sub>4<\/jats:sub>) is a potent pterin\u2010site inhibitor of nitric oxide synthases (NOS). Although 4\u2010ABH<jats:sub>4<\/jats:sub> does not exhibit selectivity between purified NOS isoforms, a pronounced selectivity of the drug towards inducible NOS (iNOS) is apparent in intact cells. This work was carried out to investigate the potential iNOS selectivity of 4\u2010ABH<jats:sub>4<\/jats:sub> in isolated pig pulmonary and coronary arteries.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Endothelium\u2010dependent relaxations of pig pulmonary and coronary artery strips to bradykinin or calcium ionophore A23187 were inhibited by 4\u2010ABH<jats:sub>4<\/jats:sub> in a concentration\u2010dependent manner. Half\u2010maximal inhibition was observed at 60\u201365\u2003\u03bc<jats:sc>M<\/jats:sc> (pulmonary artery) and 200\u2013250\u2003\u03bc<jats:sc>M<\/jats:sc> 4\u2010ABH<jats:sub>4<\/jats:sub> (coronary artery).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pig coronary artery strips precontracted with 0.1\u2003\u03bc<jats:sc>M<\/jats:sc> 9, 11\u2010dideoxy\u20109, 11\u2010methanoepoxy\u2010prosta\u2010glandin F<jats:sub>2\u03b1<\/jats:sub> (U46619) showed a time\u2010dependent relaxation (monitored for up to 18\u2003h) upon incubation with 1\u2003\u03bcg\u2003ml<jats:sup>\u22121<\/jats:sup> lipopolysaccharide (LPS). Addition of 10\u2003\u03bc<jats:sc>M<\/jats:sc> 4\u2010ABH<jats:sub>4<\/jats:sub> 1\u2003h after LPS led to a pronounced inhibition of the LPS\u2010triggered relaxation, whereas the pterin antagonist had no effect when given4\u2003h after LPS.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Incubation of pulmonary and coronary artery strips with 1\u2003\u03bcg\u2003ml<jats:sup>\u22121<\/jats:sup> LPS attenuated contractile responses to norepinephrine (1\u2003\u03bc<jats:sc>M<\/jats:sc>) and U46619 (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>). This hyporeactivity of the blood vessels to vasoconstrictor agents was inhibited by 4\u2010ABH<jats:sub>4<\/jats:sub> in a concentration\u2010dependent manner [IC<jats:sub>50<\/jats:sub>=17.5\u00b15.9\u2003\u03bc<jats:sc>M<\/jats:sc> (pulmonary artery) and 20.7\u00b13\u2003\u03bc<jats:sc>M<\/jats:sc> (coronary artery)]. The effect of 0.1\u2003m<jats:sc>M<\/jats:sc> 4\u2010ABH<jats:sub>4<\/jats:sub> was antagonized by coincubation with 0.1\u2003m<jats:sc>M<\/jats:sc> sepiapterin, which is known to supply intracellular BH<jats:sub>4<\/jats:sub> <jats:italic>via<\/jats:italic> a salvage pathway.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results demonstrate that 4\u2010ABH<jats:sub>4<\/jats:sub> is a fairly selective inhibitor of iNOS in an <jats:italic>in vitro<\/jats:italic> model of endotoxaemia, suggesting that this drug and\/or related pterin\u2010site NOS inhibitors may be useful to increase blood pressure in severe infections associated with a loss of vascular responsiveness to constrictor agents caused by endotoxin\u2010triggered iNOS induction in the vasculature.<\/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>, 1757\u20131765; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703752\">10.1038\/sj.bjp.0703752<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703752","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:02:25Z","timestamp":1106946145000},"page":"1757-1765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of endotoxin\u2010induced vascular hyporeactivity by 4\u2010amino\u2010tetrahydrobiopterin"],"prefix":"10.1111","volume":"131","author":[{"given":"Hanan D","family":"Gibraeil","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Dittrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samira","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Mayer","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":"10.1097\/00003246-199804000-00012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(98)80125-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-200005000-00007"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.50.33142"},{"key":"e_1_2_7_6_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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