{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:49:14Z","timestamp":1783478954571,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2950,"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":[[2001,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The selective carbonic anhydrase inhibitor acetazolamide is known to increase blood flow in several organs. Acetazolamide directly dilates isolated resistance arteries associated with activation of calcium\u2010activated potassium (K<jats:sub>Ca<\/jats:sub>) channels. We examined both the presence and mechanism of the direct vascular action of acetazolamide <jats:italic>in vivo<\/jats:italic> in humans.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Forearm vasodilator responses of 30 healthy volunteers to infusion of placebo and increasing doses of acetazolamide (1\u20103\u201010\u2003mg\u2003min<jats:sup>\u22121<\/jats:sup>\u2003dl<jats:sup>\u22121<\/jats:sup>) into the brachial artery were recorded by venous occlusion plethysmography, before and after local administration of <jats:sc>L<\/jats:sc>\u2010NMMA (0.2\u2003mg\u2003min<jats:sup>\u22121<\/jats:sup>\u2003dl<jats:sup>\u22121<\/jats:sup>, an inhibitor of NO\u2010synthase, <jats:italic>n<\/jats:italic>=6), indomethacin (5.0\u2003\u03bcg\u2003min<jats:sup>\u22121<\/jats:sup>\u2003dl<jats:sup>\u22121<\/jats:sup>, an inhibitor of prostaglandin synthesis, <jats:italic>n<\/jats:italic>=6), glibenclamide (10\u2003\u03bcg\u2003min<jats:sup>\u22121<\/jats:sup>\u2003dl<jats:sup>\u22121<\/jats:sup>, an inhibitor of K<jats:sub>ATP<\/jats:sub> channels, <jats:italic>n<\/jats:italic>=6), tetraethylammonium (0.1\u2003mg\u2003min<jats:sup>\u22121<\/jats:sup>\u2003dl<jats:sup>\u22121<\/jats:sup>, an inhibitor of K<jats:sub>Ca<\/jats:sub> channels, <jats:italic>n<\/jats:italic>=6) or placebo (NaCl 0.9%, <jats:italic>n<\/jats:italic>=6). Lower dosages of acetazolamide did not affect vascular tone (<jats:italic>n<\/jats:italic>=6).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Acetazolamide infusions increased forearm blood flow from 2.41\u00b10.17 to 2.99\u00b10.18, 4.09\u00b10.26 and 6.77\u00b10.49\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup>\u2003dl<jats:sup>\u22121<\/jats:sup> in the infused forearm (<jats:italic>P<\/jats:italic>&lt;0.001), with no significant changes in the non\u2010infused forearm, blood pressure or heart rate. Acetazolamide\u2010induced vasodilation was not inhibited by <jats:sc>L<\/jats:sc>\u2010NMMA, indomethacin, or glibenclamide but was significantly attenuated by TEA (vasodilation: 23\u00b16, 82\u00b119, 241\u00b138% versus 27\u00b18, 44\u00b122, 42\u00b135%).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that acetazolamide exerts a direct vasodilator effect <jats:italic>in vivo<\/jats:italic> in humans mediated by vascular K<jats:sub>Ca<\/jats:sub> channel activation. This makes acetazolamide the first drug known that specifically modulates this channel.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>132<\/jats:bold>, 443\u2013450; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703825\">10.1038\/sj.bjp.0703825<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703825","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:09:20Z","timestamp":1106946560000},"page":"443-450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["<i>In vivo<\/i> evidence for K<sub>Ca<\/sub> channel opening properties of acetazolamide in the human vasculature"],"prefix":"10.1111","volume":"132","author":[{"given":"Peter","family":"Pickkers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alun D","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans G M","family":"Russel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Thien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Smits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.25.5.918"},{"key":"e_1_2_7_3_1","first-page":"525","article-title":"The use of tetraethylammonium in peripheral vascular disease and causalgic states","volume":"20","author":"BERRY R.L.","year":"1946","journal-title":"Surgery"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.65.1.422"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1007\/BF00400658","article-title":"Interaction of sulphonylurea derivatives with vascular ATP\u2010sensitive potassium channels in humans","volume":"39","author":"BIJLSTRA P.J.","year":"1996","journal-title":"Diabetologia"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1373909"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00218-6"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199407000-00024"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115481"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1152\/ajplegacy.1967.213.5.1102","article-title":"Local effects of O2 and CO2 on limb, renal, and coronary vascular resistances","volume":"213","author":"DAUGHERTY R.M.","year":"1967","journal-title":"Am. 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