{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:35:06Z","timestamp":1789410906498,"version":"build-2803163510"},"reference-count":96,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"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":["HL\u2010162856"],"award-info":[{"award-number":["HL\u2010162856"]}],"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":["HL\u2010116579"],"award-info":[{"award-number":["HL\u2010116579"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["06637"],"award-info":[{"award-number":["06637"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004489","name":"Mitacs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004489","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"\n Abstract<\/jats:title>\n \n Sympathetic activation arising from both the peripheral chemoreflex in hypoxia and muscle metaboreflex during exercise mediate an increase in pulmonary artery systolic pressure (PASP). We tested the hypothesis that coactivation of the chemoreflex and metaboreflex would augment the PASP response, as has been shown previously for heart rate and ventilation. We conducted two experimental studies: (i) a laboratory study (\n n<\/jats:italic>\n \u00a0=\u00a015) in normoxia and acute isocapnic hypoxia (45\u00a0mmHg ) and (ii) a field study (\n n<\/jats:italic>\n \u00a0=\u00a014) at sea level (344\u00a0m) and after 4\u20136\u00a0days of acclimatisation to high altitude (3800\u00a0m). In both studies, participants performed 3\u00a0min of isometric handgrip at 30% of maximal voluntary contraction followed by 3\u00a0min of post\u2010exercise circulatory occlusion (PECO). PASP was assessed via transthoracic echocardiography. In Study 1, isocapnic hypoxia reduced (44.3\u00a0\u00b1\u00a05.3\u00a0mHg;\n P\u00a0<\/jats:italic>\n <\u00a00.001) but maintained (36.8\u00a0\u00b1\u00a02.3;\n P<\/jats:italic>\n \u00a0=\u00a00.931) compared to normoxia. Both PECO (+5.3\u00a0\u00b1\u00a05.3\u00a0mmHg;\n P<\/jats:italic>\n \u00a0=\u00a00.044) and hypoxia (+4.0\u00a0\u00b1\u00a02.0\u00a0mmHg;\n P<\/jats:italic>\n \u00a0=\u00a00.016) elevated PASP from baseline, whereas combined hypoxic PECO further increased PASP (+8.4\u00a0\u00b1\u00a03.7\u00a0mmHg,\n P<\/jats:italic>\n \u00a0=\u00a00.009). These responses were unaltered following acclimatisation to 3800\u00a0m in Study 2. Importantly, irrespective of the duration of hypoxic exposure and thus the degree of carotid body stimulation, the sum of the individual responses to hypoxia and PECO was not different compared to the combined hypoxic PECO stimulus in either acute (\n P<\/jats:italic>\n \u00a0=\u00a00.806) or chronic hypoxia (\n P<\/jats:italic>\n \u00a0=\u00a00.896). Therefore, although both chemoreflex activation with hypoxia and metaboreflex activation with PECO increase PASP, their coactivation results in an additive, not synergistic, response.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Activation of the peripheral chemoreflex (e.g. hypoxia) and muscle metaboreflex (e.g. exercise) both increase heart rate, arterial pressure, ventilation and pulmonary pressure.<\/jats:p>\n <\/jats:list-item>\n \n There is evidence of an augmented muscle metaboreflex response for heart rate and ventilation in acute hypoxia, but whether the same effect is seen in the pulmonary vasculature has not been explored.<\/jats:p>\n <\/jats:list-item>\n \n We completed two experimental studies where pulmonary artery systolic pressure (PASP) was assessed during post\u2010exercise circulatory occlusion (PECO) in response to acute isocapnic hypoxia and following acclimatisation to high altitude hypoxia (3800\u00a0m).<\/jats:p>\n <\/jats:list-item>\n \n Independent activation of the chemoreflex at rest and metaboreflex during PECO elevated PASP in both acute and chronic hypoxia.<\/jats:p>\n <\/jats:list-item>\n \n When combined, metaboreflex activation with PECO and chemoreflex activation with hypoxia have an additive but not interactive effect on PASP, irrespective of the duration of hypoxic exposure.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp290512","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T10:38:34Z","timestamp":1781692714000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The influence of metaboreflex activation on pulmonary pressure with combined chemoreflex activation in acute and chronic hypoxia"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9416-966X","authenticated-orcid":false,"given":"Lauren E.","family":"Maier","sequence":"first","affiliation":[{"name":"Cardiff School of Sport and Health Sciences Cardiff Metropolitan University Cardiff Wales UK"},{"name":"Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences University of British Columbia Okanagan Kelowna Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4053-2410","authenticated-orcid":false,"given":"Elliott J.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Cardiff School of Sport and Health Sciences Cardiff Metropolitan University Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2965-6081","authenticated-orcid":false,"given":"Andrew","family":"Douglas","sequence":"additional","affiliation":[{"name":"Cardiff School of Sport and Health Sciences Cardiff Metropolitan University Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0234-1426","authenticated-orcid":false,"given":"Jack","family":"Talbot","sequence":"additional","affiliation":[{"name":"Cardiff School of Sport and Health Sciences Cardiff Metropolitan University Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1571-9168","authenticated-orcid":false,"given":"Alexandra","family":"Williams","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences University of British Columbia Okanagan Kelowna Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4244-8220","authenticated-orcid":false,"given":"Jonathan","family":"Moore","sequence":"additional","affiliation":[{"name":"Institute for Applied Human Physiology, Department of Sport and Exercise Sciences, School of Psychology and Sports Science, College of Medicine and Health Bangor University Bangor Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig D.","family":"Steinback","sequence":"additional","affiliation":[{"name":"Neurovascular Health Lab, Faculty of Kinesiology, Sport, and Recreation University of Alberta Edmonton AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7439-1372","authenticated-orcid":false,"given":"Liam D.","family":"Corr","sequence":"additional","affiliation":[{"name":"Cardiff School of Sport and Health Sciences Cardiff Metropolitan University Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0187-0123","authenticated-orcid":false,"given":"Zoe H.","family":"Adams","sequence":"additional","affiliation":[{"name":"Cardiff School of Sport and Health Sciences Cardiff Metropolitan University Cardiff Wales UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4767-7249","authenticated-orcid":false,"given":"Fabio Giuseppe","family":"Laginestra","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4012-8880","authenticated-orcid":false,"given":"Markus","family":"Amann","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6560-222X","authenticated-orcid":false,"given":"Philip N.","family":"Ainslie","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences University of British Columbia Okanagan Kelowna 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