{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:57:20Z","timestamp":1788411440428,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T00:00:00Z","timestamp":1748649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Metabolic inhibition of sympathetic vasoconstriction (functional sympatholysis) is essential for adequate perfusion of skeletal muscle during exercise. Neuropeptide Y (NPY) is a neurotransmitter that elicits potent vasoconstriction and is co\u2010released with noradrenaline during sympathoexcitation. NPY is released from sympathetic nerves during exercise; however, no study has assessed whether NPY\u2010mediated vasoconstriction is sensitive to metabolic inhibition in humans. We tested the hypothesis that post\u2010junctional NPY\u2010mediated vasoconstriction would be sensitive to metabolic inhibition during handgrip exercise to a similar degree as \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenergic vasoconstriction. In 12 healthy adults (seven male, age: 30\u00a0\u00b1\u00a07\u00a0years, body mass index: 24.9\u00a0\u00b1\u00a03\u00a0kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) we measured forearm blood flow (Doppler ultrasound), blood pressure (brachial artery catheter) and heart rate, and calculated changes in forearm vascular conductance (FVC) to local intra\u2010arterial infusions of phenylephrine (PE; \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010agonist) or NPY (Y1R\u2010agonist) during: (1) intra\u2010arterial infusion of sodium nitroprusside (SNP; nitric oxide donor), a non\u2010metabolic vasodilatory control, and (2) dynamic rhythmic handgrip exercise (EX; 15% maximal voluntary contraction). As expected, the vasoconstrictor response to PE was attenuated during handgrip exercise compared to SNP (\u0394FVC: SNP: \u221244\u00a0\u00b1\u00a025%\n                      <jats:italic>vs<\/jats:italic>\n                      . EX: \u221217\u00a0\u00b1\u00a09%;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.002). Similarly, NPY\u2010mediated vasoconstriction was blunted during handgrip exercise compared to SNP (\u0394FVC: SNP: \u221232\u00a0\u00b1\u00a022%\n                      <jats:italic>vs<\/jats:italic>\n                      . EX: \u221211\u00a0\u00b1\u00a07%;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.029). There was no difference in the magnitude of sympatholysis between PE and NPY (PE: 68\u00a0\u00b1\u00a018\n                      <jats:italic>vs<\/jats:italic>\n                      . NPY: 52\u00a0\u00b1\u00a034%;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.28). NPY\u2010mediated vasoconstriction is sensitive to metabolic inhibition in humans, and the magnitude of sympatholysis is not different from \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenergic vasoconstriction.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16764-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Neuropeptide Y (NPY) is a neurotransmitter that is co\u2010released from sympathetic nerve terminals and elicits potent vasoconstriction, particularly during periods of sympathoexcitation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>NPY is released from sympathetic nerves during exercise, but it is currently unclear whether NPY\u2010mediated vasoconstriction is sensitive to metabolic inhibition in humans (i.e. functional sympatholysis).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            For the first time we have shown that NPY\u2010mediated vasoconstriction is sensitive to metabolic inhibition during exercise in healthy adults, and that the magnitude of inhibition is similar to the inhibition observed for \u03b1\n                            <jats:sub>1<\/jats:sub>\n                            \u2010adrenergic mediated vasoconstriction.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp288412","type":"journal-article","created":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T10:38:26Z","timestamp":1748687906000},"page":"3329-3340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional sympatholysis of neuropeptide Y\u2010mediated vasoconstriction in humans"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4200-3790","authenticated-orcid":false,"given":"Denis J.","family":"Wakeham","sequence":"first","affiliation":[{"name":"Institute for Exercise and Environmental Medicine Texas Health Presbyterian Hospital  Dallas TX USA"},{"name":"Department of Internal Medicine The University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3181-6961","authenticated-orcid":false,"given":"Sarah L.","family":"Hissen","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine Texas Health Presbyterian Hospital  Dallas TX USA"},{"name":"Department of Applied Clinical Research The University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"MacNamara","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine Texas Health Presbyterian Hospital  Dallas TX USA"},{"name":"Department of Internal Medicine The University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Applied Clinical Research The University of Texas Southwestern Medical Center  Dallas TX USA"},{"name":"Department of Applied Physiology and Sport Management Southern Methodist University  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0115-0743","authenticated-orcid":false,"given":"Paul J.","family":"Fadel","sequence":"additional","affiliation":[{"name":"Department of Kinesiology The University of Texas at Arlington  Arlington TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9064-7251","authenticated-orcid":false,"given":"Benjamin D.","family":"Levine","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine Texas Health Presbyterian Hospital  Dallas TX USA"},{"name":"Department of Internal Medicine The University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Christopher M.","family":"Hearon","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine Texas Health Presbyterian Hospital  Dallas TX USA"},{"name":"Department of Applied Clinical Research The University of Texas Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,31]]},"reference":[{"issue":"3","key":"e_1_2_6_2_1","first-page":"318","article-title":"Coronary sinus neuropeptide Y levels and adverse outcomes in patients with stable chronic heart failure","volume":"5","author":"Ajijola O. A.","year":"2020","journal-title":"Journal of the American Medical Association Cardiology"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00427.2005"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00071.2004"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-53491-0.00003-1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP285370"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.83.3.774"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(85)90433-9"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(199701)25:1<44::AID-SYN6>3.0.CO;2-F"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0700908"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2022.102232"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00842.2012"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.024850"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11038"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00208.2020"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270593"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2019.04.002"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272829"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP279462"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP274532"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz115"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00157.2009"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11498"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00723.2003"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201x.1999.00475.x"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz852"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.15208"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.154252"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.28.3.483"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-7952(06)80018-2"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(85)91837-6"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(86)90020-0"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(83)90401-9"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.3085"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(86)90089-5"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.273722"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.240093"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/080370500453465"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2011.059584"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(87)90251-7"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475-097X.1989.tb00957.x"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475-097X.1986.tb00789.x"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-0115(87)90173-X"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.11.3.370"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-0115(88)90234-0"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.241026"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008040402"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(91)90849-L"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00936.2010"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00230.2022"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00380.2018"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.014431"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.203026"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP288412","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T13:31:32Z","timestamp":1749475892000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP288412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,31]]},"references-count":52,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1113\/JP288412"],"URL":"https:\/\/doi.org\/10.1113\/jp288412","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,31]]},"assertion":[{"value":"2025-01-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}