{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:03:07Z","timestamp":1773932587978,"version":"3.50.1"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,12,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Uric acid (\n              <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n              ) is a plasmatic antioxidant that has possible effects on blood pressure. The effects of\n              <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n              on endothelial function are unclear. We hypothesize that endothelial function is not impaired unless significant\n              <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n              depletion is achieved through selective xanthine oxidase inhibition with febuxostat and recombinant uricase (rasburicase).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Microvascular hyperemia, induced by iontophoresis of acetylcholine and sodium nitroprusside, and heating\u2010induced local hyperemia after iontophoresis of saline and a specific\n              <jats:styled-content style=\"fixed-case\">nitric oxide<\/jats:styled-content>\n              synthase inhibitor were assessed by laser Doppler imaging. Blood pressure and renin\u2010angiotensin system markers were measured, and arterial stiffness was assessed. CRP (C\u2010reactive protein), allantoin, chlorotyrosine\/tyrosine ratio, homocitrulline\/lysine ratio, myeloperoxidase activity, malondialdehyde, and interleukin\u20108 were used to characterize inflammation and oxidative stress. Seventeen young healthy men were enrolled in a randomized, double\u2010blind, placebo\u2010controlled, 3\u2010way crossover study. The 3 compared conditions were placebo, febuxostat alone, and febuxostat together with rasburicase. The allantoin (\u03bcmol\/L)\/\n              <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n              (\u03bcmol\/L) ratio differed between sessions (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001). During the febuxostat\u2010rasburicase session, heating\u2010induced hyperemia became altered in the presence of\n              <jats:styled-content style=\"fixed-case\">nitric oxide<\/jats:styled-content>\n              synthase inhibition; and systolic blood pressure, angiotensin\n              <jats:styled-content style=\"fixed-case\">II,<\/jats:styled-content>\n              and myeloperoxidase activity decreased (\n              <jats:italic>P<\/jats:italic>\n              \u22640.03 versus febuxostat). The aldosterone concentration decreased in the febuxostat\u2010rasburicase group (\n              <jats:italic>P<\/jats:italic>\n              =0.01). Malondialdehyde increased when\n              <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n              concentration decreased (both\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01 for febuxostat and febuxostat\u2010rasburicase versus placebo). Other parameters remained unchanged.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              A large and short\u2010term decrease in\n              <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n              in humans alters heat\u2010induced endothelium\u2010dependent microvascular vasodilation, slightly reduces systolic blood pressure through renin\u2010angiotensin system activity reduction, and markedly reduces myeloperoxidase activity when compared with moderate\n              <jats:styled-content style=\"fixed-case\">UA<\/jats:styled-content>\n              reduction. A moderate or severe hypouricemia leads to an increase in lipid peroxidation through loss of antioxidant capacity of plasma.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Clinical Trial Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">URL<\/jats:styled-content>\n              :\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier:\n              <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>\n              03395977.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.013130","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T10:00:24Z","timestamp":1574416824000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Severe Hypouricemia Impairs Endothelium\u2010Dependent Vasodilatation and Reduces Blood Pressure in Healthy Young Men: A Randomized, Placebo\u2010Controlled, and Crossover Study"],"prefix":"10.1161","volume":"8","author":[{"given":"Benjamin","family":"De Becker","sequence":"first","affiliation":[{"name":"Department of Cardiology Erasme Hospital Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Coremans","sequence":"additional","affiliation":[{"name":"Department A: Research in Drug Development (RD3)\u2013Pharmacognosy, Bioanalysis and Drug Discovery and Analytical Platform of the Faculty of Pharmacy Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Chaumont","sequence":"additional","affiliation":[{"name":"Department of Cardiology Erasme Hospital Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9dric","family":"Delporte","sequence":"additional","affiliation":[{"name":"Department A: Research in Drug Development (RD3)\u2013Pharmacognosy, Bioanalysis and Drug Discovery and Analytical Platform of the Faculty of Pharmacy Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Van Antwerpen","sequence":"additional","affiliation":[{"name":"Department A: Research in Drug Development (RD3)\u2013Pharmacognosy, Bioanalysis and Drug Discovery and Analytical Platform of the Faculty of Pharmacy Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Franck","sequence":"additional","affiliation":[{"name":"Centre of Oxygen, Research and Development Institute of Chemistry B 6a University of Li\u00e8ge\u2013Sart Tilman Li\u00e8ge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Medicine (ULB 222) Medicine Faculty Universit\u00e9 Libre de Bruxelles Centre Hospitalier Universitaire de Charleroi, Hopital Vesale Montigny\u2010le\u2010Tilleul Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karim","family":"Zouaoui Boudjeltia","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Medicine (ULB 222) Medicine Faculty Universit\u00e9 Libre de Bruxelles Centre Hospitalier Universitaire de Charleroi, Hopital Vesale Montigny\u2010le\u2010Tilleul Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Cullus","sequence":"additional","affiliation":[{"name":"Biostatistics Department Medicine Faculty Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"van de Borne","sequence":"additional","affiliation":[{"name":"Department of Cardiology Erasme Hospital Universit\u00e9 Libre de Bruxelles Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000701"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.36.6.1072"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes223"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001980"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00360-008-0291-7"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20344"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000033"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-14-1267"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-15-0232"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(92)90321-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199309000-00013"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00370582"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(93)90143-I"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.651117"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0817-7"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0283"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.2147\/VHRM.S4265"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.10.840"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1710895"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201916"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0466-4"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.00991"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e3182858f81"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200011000-00014"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00407.2010"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2012.06.044"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2015.1027197"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e318193c35d"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.236398"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2009.05141.x"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106830"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00201.2015"},{"key":"e_1_3_2_34_2","volume-title":"The Endothelium Part 2: EDHF\u2010Mediated Responses \u201cThe Classical Pathway.\u201d","author":"F\u00e9l\u00e9tou M","year":"2011","unstructured":"F\u00e9l\u00e9tou M. The Endothelium Part 2: EDHF\u2010Mediated Responses \u201cThe Classical Pathway.\u201d San Rafael (CA): Morgan & Claypool Life Sciences Publishers Series INTEGRATED; 2011."},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-010-0817-1"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(81)90094-0"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2017.03.003"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2016.03.001"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00645.2016"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.2337\/dbi16-0026"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M061697"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12255"},{"key":"e_1_3_2_43_2","first-page":"690135","article-title":"Antihypertensive action of allantoin in animals","volume":"2014","author":"Chen MF","year":"2014","unstructured":"Chen MF, Tsai JT, Chen LJ, Wu TP, Yang JJ, Te Yin L, Yang YL, Chiang TA, Lu HL, Wu MC. Antihypertensive action of allantoin in animals. Biomed Res Int. 2014;2014:690135.","journal-title":"Biomed Res Int"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu218"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.11.6858"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1991.tb03204.x"},{"key":"e_1_3_2_47_2","first-page":"37","article-title":"Free radical scavenging, DNA protection, and inhibition of lipid peroxidation mediated by uric acid","volume":"35","author":"Stinefelt B","year":"2005","unstructured":"Stinefelt B, Leonard SS, Blemings KP, Shi X, Klandorf H. Free radical scavenging, DNA protection, and inhibition of lipid peroxidation mediated by uric acid. Ann Clin Lab Sci. 2005;35:37\u201345.","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.2003.pto930606.x"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.106.480699"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000022140.61460.1D"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.35.3.746"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.4.1118"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1080\/15257770802138558"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-018-0900-0"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3282f240bf"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.4135"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2449-0"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/jch.12353"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.119.013130","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T10:56:52Z","timestamp":1715597812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.119.013130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,3]]},"references-count":57,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2019,12,3]]}},"alternative-id":["10.1161\/JAHA.119.013130"],"URL":"https:\/\/doi.org\/10.1161\/jaha.119.013130","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,3]]},"assertion":[{"value":"2019-07-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e013130"}}