{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T16:19:46Z","timestamp":1777565986697,"version":"3.51.4"},"reference-count":74,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL161160"],"award-info":[{"award-number":["R01HL161160"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL156594"],"award-info":[{"award-number":["R01HL156594"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL156513"],"award-info":[{"award-number":["R01HL156513"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Controversy exists on which metabolites determine the exaggerated exercise pressor reflex (EPR) in peripheral artery disease (PAD). In decerebrated rats, we investigated the role played by lactate and hydrogen ions in a model of PAD, which was simulated by ligating the femoral artery for 72\u2009h before the start of the experiment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Production of lactate and hydrogen ions by the contracting hindlimb muscles was manipulated by knocking out the myophosphorylase gene (pygm). In both knockout (pygm\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913; 6\u2010females) and wild\u2010type rats (pygm\n                      <jats:sup>+\/+<\/jats:sup>\n                      ;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914; 7\u2010females), the EPR was evoked by statically contracting the triceps\u2010surae muscles. Blood pressure, tension, and renal sympathetic nerve activity were measured. Responsiveness of the metabolic component of the EPR was evaluated by intra\u2010arterial injections of lactic acid and diprotonated phosphate solutions. Responsiveness of the mechanical component of the EPR was evaluated by stretching the calcaneal tendon. In each rat, the pressor responses evoked from the freely perfused triceps\u2010surae muscles were compared to those evoked from the contralateral ischemic triceps\u2010surae muscles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In pygm\n                      <jats:sup>+\/+<\/jats:sup>\n                      rats whose femoral artery was ligated, static contraction, lactic\u2010acid injection and diprotonated phosphate injection evoked pressor responses that were 88%, 22%, and 58% greater than those evoked from muscles whose femoral arteries were freely perfused. In pygm\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      rats, ligation of the femoral artery for 72\u2009h had no effect. In both groups, 72\u2009h of femoral artery ligation exacerbated the pressor response to passive stretch.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Lactate and hydrogen\u2010ions accumulation in contracting myocytes plays a key role in exaggerating the metabolic component of the EPR evoked from hindlimb muscles with chronically\u2010ligated femoral arteries.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70172","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:33:42Z","timestamp":1771238022000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Myophosphorylase Knock Out Prevents the Exaggerated Exercise Pressor Reflex in Rats With Simulated Peripheral Artery Disease"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3531-4678","authenticated-orcid":false,"given":"Guillaume P.","family":"Ducrocq","sequence":"first","affiliation":[{"name":"Heart and Vascular Institute Penn State College of Medicine  Hershey Pennsylvania USA"},{"name":"Facult\u00e9 de M\u00e9decine, UR3072 \u00abMitochondrie, Stress Oxydant et Plasticit\u00e9 Musculaire\u00bb Universit\u00e9 de Strasbourg  Strasbourg France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Anselmi","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Ruiz\u2010Velasco","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute Penn State College of Medicine  Hershey Pennsylvania USA"},{"name":"Department of Anesthesiology and Perioperative Medicine Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc P.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2018.05.033"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(91)90014-T"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00641.2017"},{"key":"e_1_2_11_5_1","first-page":"47","article-title":"Correlation of Function and Energy Metabolism in Rat Ischemic Skeletal Muscle by 31P\u2010NMR Spectroscopy: Effects of Torbafylline","volume":"24","author":"Koch H.","year":"1993","journal-title":"Journal of Medicine"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01725196"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1991.71.5.1837"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/000331979905000502"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475-097X.2007.00720.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.241281"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00141.2010"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1971.sp009498"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1972.sp009887"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4613-0579-8_3"},{"key":"e_1_2_11_15_1","first-page":"231","article-title":"Free Nerve Endings in Skeletal Muscle of the Cat","volume":"105","author":"Stacey M. J.","year":"1969","journal-title":"Journal of Anatomy"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00288.2015"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00974.2015"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00137.2020"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP091616"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00399.2019"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.247973"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00188.2011"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.217851"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1113\/jp286488"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00257.2020"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.65.4.1539"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00942.2016"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.03.043"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.64.6.2306"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00398.2004"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.4.H1890"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2012.064840"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00961.x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.64.3.592"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.4097\/kja.d.18.00242"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.316.7139.1236"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1525\/ae.2004.31.4.475"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00762.2013"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2012.00247"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2014.10.014"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00274.2022"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00926.2012"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP285267"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00735.2004"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP275058"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00612.2010"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.70457"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00630.2015"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.029"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2005001100001"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.146442"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-24-10662.2002"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3529"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn0901-869"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)01130-3"},{"key":"e_1_2_11_56_1","article-title":"Inorganic Phosphate and Lactate Potentiate the Pressor Response to Acidic Stimuli in Rats","volume":"276","author":"Ducrocq G. P.","year":"2020","journal-title":"Experimental Physiology"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00271.2008"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/39807"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00389.2004"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.4482"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2006"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00993.x"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00174.2019"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/0741-5214(89)90081-5"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0680597"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4408-12.2013"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309468200"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.15933"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00617.2012"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1990.68.3.861"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.193227"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271714"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1113\/jp289092"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1113\/jp286118"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00794.2020"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.70172","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apha.70172","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.70172","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:49:19Z","timestamp":1777402159000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.70172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,16]]},"references-count":74,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/apha.70172"],"URL":"https:\/\/doi.org\/10.1111\/apha.70172","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,16]]},"assertion":[{"value":"2025-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70172"}}