{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T04:40:18Z","timestamp":1761021618028},"reference-count":43,"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":1458,"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":[[2005,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Renal medullary blood flow is relatively insensitive to angiotensin II (Ang II)\u2010induced vasoconstriction, due partly to AT<jats:sub>1<\/jats:sub>\u2010mediated release of nitric oxide and\/or prostaglandins. AT<jats:sub>2<\/jats:sub>\u2010receptor activation appears to blunt AT<jats:sub>1<\/jats:sub>\u2010mediated vasodilatation within the medullary circulation. This could affect long\u2010term efficacy of antihypertensive pharmacotherapies targeting the renin\/angiotensin system, particularly in Ang II\u2010dependent forms of hypertension.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We tested the effects of AT<jats:sub>1<\/jats:sub>\u2010 and AT<jats:sub>2<\/jats:sub>\u2010receptor blockade on basal cortical and medullary laser Doppler flux (CLDF and MLDF), and on responses to renal arterial infusion of Ang II, in rats with 2 kidney, 1 clip (2K1C) hypertension and sham\u2010operated controls. Studies were carried out in thiobutabarbital (175\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, i.p.) anaesthetised rats, 4 weeks after clipping, or sham surgery (<jats:italic>n<\/jats:italic>=6 in each of eight groups).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Candesartan (10\u2003<jats:italic>\u03bc<\/jats:italic>g\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h<jats:sup>\u22121<\/jats:sup>, intravenous (i.v.)) reduced mean arterial pressure (\u223c17%) and increased CLDF (\u223c24%), similarly in both sham and 2K1C rats, but did not significantly affect MLDF. PD123319 (1\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h<jats:sup>\u22121<\/jats:sup>, i.v.) increased basal MLDF (19%) in 2K1C but not sham rats, without significantly affecting other variables.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In sham rats, renal arterial infusion of Ang II (1\u2013100\u2003ng\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003min<jats:sup>\u22121<\/jats:sup>) dose dependently decreased CLDF (up to 44%), but did not significantly affect MLDF. These effects were markedly blunted in 2K1C rats. After PD123319, Ang II dose dependently increased MLDF (up to 38%) in sham but not 2K1C rats. Candesartan abolished all effects of Ang II, including those seen after PD123319.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our data indicate that AT<jats:sub>1<\/jats:sub> receptors mediate medullary vasodilatation, which is opposed by AT<jats:sub>2<\/jats:sub>\u2010receptor activation. In 2K1C hypertension, AT<jats:sub>2<\/jats:sub>\u2010receptor activation tonically constricts the medullary circulation.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2005) <jats:bold>144<\/jats:bold>, 486\u2013492. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706036\">10.1038\/sj.bjp.0706036<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706036","type":"journal-article","created":{"date-parts":[[2005,1,27]],"date-time":"2005-01-27T16:01:08Z","timestamp":1106841668000},"page":"486-492","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["AT<sub>2<\/sub> receptors mediate tonic renal medullary vasoconstriction in renovascular hypertension"],"prefix":"10.1111","volume":"144","author":[{"given":"Lisa M","family":"Duke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E","family":"Widdop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle M","family":"Kett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger G","family":"Evans","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":"10.1113\/jphysiol.2001.012921"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2003.00875.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/hy09t1.096186"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.25.6.1232"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-000-0082-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.33.1.102"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1997.273.1.R1"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00701.2002"},{"key":"e_1_2_7_10_1","first-page":"169","article-title":"An improved synthesis of (S)\u20101\u2010[[4\u2010(dimethylamino)\u20103\u2010methylphenyl]methyl]\u20105\u2010(diphenylacetyl)\u20104,5,6,7\u2010tetrahydro\u20101H\u2010imidazo[4,5\u2010c]pyridine\u20106\u2010carboxylic acid, ditrifluoroacetate, dihydrate (PD123319)","volume":"1","author":"CUNDY D.","year":"2000","journal-title":"Arkivoc"},{"key":"e_1_2_7_11_1","first-page":"F417","article-title":"Angiotensin II and prostaglandins in control of vasa recta blood flow","volume":"254","author":"CUPPLES W.A.","year":"1988","journal-title":"Am. 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