{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:13:35Z","timestamp":1789910015436,"version":"4.0.1"},"reference-count":72,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T00:00:00Z","timestamp":1528416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["UO\u20101 HL 105365"],"award-info":[{"award-number":["UO\u20101 HL 105365"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>In sleep apnoea, a putative link between intermittent hypoxia and hypertension is the generation of oxygen radicals by angiotensin\u00a0II and xanthine oxidase within the chemoreflex arc and vasculature. We tested whether chemoreflex control of sympathetic outflow, hypoxic vasodilatation and blood pressure are altered by angiotensin blockade (losartan) and\/or xanthine oxidase inhibition (allopurinol).<\/jats:p>\n<\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Both drugs lowered blood pressure without altering sympathetic outflow, reducing chemoreflex sensitivity or enhancing hypoxic vasodilatation. Losartan and allopurinol are effective therapies for achieving blood pressure control in sleep apnoea.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Chemoreflex sensitization produced by chronic intermittent hypoxia in rats is attenuated by angiotensin\u00a0II type\u00a01 receptor (AT<jats:sub>1<\/jats:sub>R) blockade. Both AT<jats:sub>1<\/jats:sub>R blockade and xanthine oxidase inhibition ameliorate chronic intermittent hypoxia\u2010induced endothelial dysfunction. We hypothesized that treatment with losartan and allopurinol would reduce chemoreflex sensitivity and improve hypoxic vasodilatation in patients with obstructive sleep apnoea. Eighty\u2010six hypertensive patients with apnoea\u2013hypopnoea index \u226525\u00a0events\u00a0h<jats:sup>\u22121<\/jats:sup> and no other cardiovascular, pulmonary, renal or metabolic disease were randomly assigned to receive allopurinol, losartan or placebo for 6\u00a0weeks. Treatment with other medications and\/or continuous positive airway pressure remained unchanged. Tests of chemoreflex sensitivity and hypoxic vasodilatation were performed during wakefulness before and after treatment. Ventilation (pneumotachography), muscle sympathetic nerve activity (microneurography), heart rate (electrocardiography), arterial oxygen saturation (pulse oximetry), blood pressure (sphygmomanometry), forearm blood flow (venous occlusion plethysmography) and cerebral flow velocity (transcranial Doppler ultrasound) were measured during eupnoeic breathing and graded reductions in inspired O<jats:sub>2<\/jats:sub> tension. Losartan and allopurinol lowered arterial pressure measured during eupnoeic breathing and exposure to acute hypoxia. Neither drug altered the slopes of ventilatory, sympathetic or cardiovascular responses to acute hypoxia. We conclude that losartan and allopurinol are viable pharmacotherapeutic adjuncts for achieving blood pressure control in hypertensive obstructive sleep apnoea patients, even those who are adequately treated with continuous positive airway pressure.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep087006","type":"journal-article","created":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T12:09:59Z","timestamp":1526040599000},"page":"941-955","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Effects of losartan and allopurinol on cardiorespiratory regulation in obstructive sleep apnoea"],"prefix":"10.1113","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2082-3963","authenticated-orcid":false,"given":"Barbara J.","family":"Morgan","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Rehabilitation University of Wisconsin\u2010Madison  Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Teodorescu","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Wisconsin\u2010Madison  Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Pegelow","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin\u2010Madison  Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily R.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Pharmacy Practice Division, School of Pharmacy University of Wisconsin\u2010Madison  Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin L.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Pharmacy Practice Division, School of Pharmacy University of Wisconsin\u2010Madison  Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Plante","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Wisconsin\u2010Madison  Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Gapinski","sequence":"additional","affiliation":[{"name":"Aurora BayCare Medical Center  Green Bay WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J.","family":"Hetzel","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics, School of Medicine and Public Health University of Wisconsin\u2010Madison  Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Dopp","sequence":"additional","affiliation":[{"name":"Pharmacy Practice Division, School of Pharmacy University of Wisconsin\u2010Madison  Madison WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1848375"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000042706.47107.7A"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.2172"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2004.08.079"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.129.6.1459"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.103.6.1763"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199605000-00006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.202598"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00409.2013"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07255"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00158109"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00434"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2869.2007.00602.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000329341"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.06.00101005"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.02.033"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.300.8.924"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11325-011-0481-5"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1992.72.5.1978"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.19.6.555"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-199305000-00006"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.5310"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000034"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a070026"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00090"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(03)00917-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.1999.02995.x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/jch.12472"},{"key":"e_1_2_8_30_1","volume-title":"The AASM manual for the scoring of sleep and associated events: Rules, terminology, and technical specifications","author":"Iber C.","year":"2007"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.06-2580"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00241.2004"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpx174"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301-5629(86)90139-0"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00885.2005"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2014.07.003"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00629.2014"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2016.11.001"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00727.2011"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2014.082826"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2010.02.003"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2008.10.013"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2012.05.025"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.8.862"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00015.2016"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2016.09.001"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075838"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119762"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.9.1183"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200912-1803OC"},{"key":"e_1_2_8_51_1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1093\/sleep\/28.5.604","article-title":"Diurnal and obstructive sleep apnea influences on arterial stiffness and central blood pressure in men","volume":"28","author":"Phillips C.","year":"2005","journal-title":"Sleep"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00994.2005"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00683.2003"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200905-0671OC"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP085624"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140039"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2016.1243803"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.66.6.2778"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200903-0393OC"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.06.00062805"},{"key":"e_1_2_8_61_1","first-page":"1155","article-title":"Benefits of allopurinol treatment on blood pressure and renal function in patients with early stage of chronic kidney disease","volume":"98","author":"Satirapoj B.","year":"2015","journal-title":"Journal of the Medical Association of Thailand"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1981.50.6.1300"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00162.2015"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.31.7.1672"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.67.5.2095"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1080\/AC.71.3.3152087"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00204209"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201505-0998OC"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00345.2014"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1979.59.4.919"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.153.4.8616563"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200708-119MG"},{"key":"e_1_2_8_73_1","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1016\/j.jacc.2017.11.006","article-title":"2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: A report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"71","author":"Whelton P. K.","year":"2018","journal-title":"Journal of the American College of Cardiology"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FEP087006","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP087006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T19:46:29Z","timestamp":1695411989000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP087006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,8]]},"references-count":72,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1113\/EP087006"],"URL":"https:\/\/doi.org\/10.1113\/ep087006","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,8]]},"assertion":[{"value":"2018-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}