{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T03:43:47Z","timestamp":1774323827741,"version":"3.50.1"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":4051,"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":[[1998,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item>\n<jats:p>In this study the role of nitric oxide synthase (NOS) in the acute activation of large conductance, Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> channels (BK channels) by internally applied <jats:italic>E. coli<\/jats:italic> lipopolysaccharide (LPS, endotoxin) was examined in vascular smooth muscle cells.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Cerebrovascular smooth muscle cells (CVSMCs) were enzymatically dispersed from the middle, posterior communicating and posterior cerebral arteries of adult Wistar rats and maintained at 4\u00b0C for 2\u20134 days before recording with standard patch\u2010clamp techniques.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Acute application of LPS (100\u2003\u03bcg\u2003ml<jats:sup>\u22121<\/jats:sup>) to inside\u2010out patches of CVSMC membrane isolated in a cell\u2010free environment rapidly and reversibly increased the open probability, P<jats:sub>o<\/jats:sub> of BK channels in these patches by 3.3\u00b10.30 fold.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Acute application of the nitric oxide (NO) donor sodium nitroprusside (SNP, 100\u2003\u03bc<jats:sc>M<\/jats:sc>) to inside\u2010out patches of CVSMC membrane, studied in the presence of intact cells, also reversibly increased P<jats:sub>o<\/jats:sub>, by some 1.8\u00b10.2 fold over control.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Kinetic analysis showed that both LPS and SNP increased P<jats:sub>o<\/jats:sub> by accelerating the rate of BK channel reopening, rather than by retarding the closure of open channels.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Neither LPS nor SNP altered the reversal potential or conductance of BK channels.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>The NOS substrate <jats:sc>L<\/jats:sc>\u2010arginine (1\u2003\u03bc<jats:sc>M<\/jats:sc>) potentiated the acute activation of BK channels by LPS, while the synthetic enantiomer <jats:sc>D<\/jats:sc>\u2010arginine (1\u2003\u03bc<jats:sc>M<\/jats:sc>) inhibited the action of LPS on BK channels.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>The acute activation of BK channels by LPS was suppressed by pre\u2010incubation of cells with N<jats:sup>\u03c9<\/jats:sup>\u2010nitro\u2010<jats:sc>L<\/jats:sc>\u2010arginine (50\u2003\u03bc<jats:sc>M<\/jats:sc>) or N\u03c9\u2010nitro\u2010L\u2010arginine methyl ester (1\u2003\u2003mM), two competitive antagonists of nitric oxide synthases. N<jats:sup>\u03c9<\/jats:sup>\u2010nitro\u2010<jats:sc>D<\/jats:sc>\u2010arginine (50\u2003\u03bc<jats:sc>M<\/jats:sc>), a poor inhibitor of NOS in <jats:italic>in vitro<\/jats:italic> assays, had no effect on BK channel activation by LPS.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>These results indicate that excised, inside\u2010out patches of CVSMC membrane exhibit a NOS\u2010like activity which is acutely activated when LPS is present at the cytoplasmic membrane surface. Possible relationships between this novel mechanism and the properties of known isoforms of nitric oxide synthase are discussed.<\/jats:p>\n<\/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>, 5\u201312; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701570\">10.1038\/sj.bjp.0701570<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701570","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:14:07Z","timestamp":1106939647000},"page":"5-12","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Internally applied endotoxin and the activation of BK channels in cerebral artery smooth muscle via a nitric oxide\u2010like pathway"],"prefix":"10.1111","volume":"123","author":[{"given":"L M","family":"Hoang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D A","family":"Mathers","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":"10.1074\/jbc.270.43.25859"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.16.7583"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1993.121"},{"key":"e_1_2_6_5_1","first-page":"R38","article-title":"Interleukin 1 and endotoxin activate soluble guanylate cyclase in vascular smooth muscle","volume":"259","author":"Beasley D.","year":"1990","journal-title":"Am. 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