{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:08:09Z","timestamp":1771459689600,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K11425"],"award-info":[{"award-number":["24K11425"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Increased blood hemoglobin concentration theoretically promotes oxygen delivery to the periphery. Clinically, in addition to recombinant human erythropoietin analogs, prolyl hydroxylase (PH) inhibitors to stabilize the expression of hypoxia\u2010inducible factor (HIF) protein were recently approved for the treatment of anemia in chronic kidney disease. However, whether the new agent helps enhance physical exercise capacity remains a matter of controversy. Treatment of C57BL\/6J mice via oral gavage with roxadustat of 30\u2009mg\/kg three times per week for 5\u2009weeks elevated the blood hemoglobin concentration, upregulated the HIF\u2010downstream gene expression of the muscle, and enhanced a high\u2010intensity exercise performance measured with a treadmill running exhaustion test, compared to those treated with vehicle, while total body weight or skeletal muscle mass was comparable. This physical effect depended on the increase in blood hemoglobin concentration, as confirmed by mice hemodiluted to control hemoglobin concentrations through phlebotomy followed by infusion of the approximate volume of phosphate\u2010buffered saline. In conclusion, oral administration of the HIF\u2010PH inhibitor to mice increased high\u2010intensity exercise capacity as well as elevated blood hemoglobin concentration. The finding implies the versatile effects on humans taking HIF\u2010PH inhibitors, as well as the risk of them being abused for blood doping.<\/jats:p>","DOI":"10.14814\/phy2.70464","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T02:31:09Z","timestamp":1752546669000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacological prolyl hydroxylase inhibition enhances high\u2010intensity exercise capacity in mice"],"prefix":"10.14814","volume":"13","author":[{"given":"Koji","family":"Takemura","sequence":"first","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoki","family":"Odawara","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8415-7889","authenticated-orcid":false,"given":"Hiroshi","family":"Nishi","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaaki","family":"Higashihara","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2479-5771","authenticated-orcid":false,"given":"Koichi","family":"Nakazato","sequence":"additional","affiliation":[{"name":"Department of Exercise Physiology Nippon Sport Science University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuharu L.","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Health Promotion Sciences Graduate School of Human Health Sciences, Tokyo Metropolitan University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naokata","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Life Sciences The University of Tokyo Graduate School of Arts and Sciences  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-7736","authenticated-orcid":false,"given":"Reiko","family":"Inagi","sequence":"additional","affiliation":[{"name":"Division of CKD Pathophysiology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuhiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaomi","family":"Nangaku","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2019.100632"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011111078"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfab191"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005768-200001000-00012"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581817737232"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg392"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.390"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2016.01.029"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.727"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13425"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002311"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00207.2006"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2012.12.003"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad483"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(17)30105-9"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-88438-7"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2024.01.005"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.02.002"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.05.009"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP085318"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202487200"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020288"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2015.193"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semradonc.2004.04.005"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12061814"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfx134"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12751"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2024.2378903"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200509265"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-013-7270-x"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016089107"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912924107"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00518-9"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.565023"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.70464","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T07:55:03Z","timestamp":1753343703000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.70464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":34,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.14814\/phy2.70464"],"URL":"https:\/\/doi.org\/10.14814\/phy2.70464","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2025-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70464"}}