{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:37:01Z","timestamp":1781239021044,"version":"3.54.1"},"reference-count":56,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"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":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      We investigated the role played by lactate and hydrogen in evoking the exercise pressor reflex (EPR) in decerebrated rats whose hindlimb muscles were either freely perfused or ischaemic. Production of lactate and hydrogen by the contracting hindlimb muscles was manipulated by knocking out the myophosphorylase gene (\n                      <jats:italic>pygm<\/jats:italic>\n                      ). In knockout rats (\n                      <jats:italic>pygm<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ;\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a013) or wild\u2010type rats (\n                      <jats:italic>pygm<\/jats:italic>\n                      <jats:sup>+\/+<\/jats:sup>\n                      ;\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a013), the EPR was evoked by isometrically contracting the triceps surae muscles. Blood pressure, tension, blood flow, renal sympathetic nerve activity and blood lactate concentrations were measured. Intramuscular metabolites and pH changes induced by the contractions were quantified by\n                      <jats:sup>31<\/jats:sup>\n                      P\u2010magnetic resonance spectroscopy (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05). In a subset of\n                      <jats:italic>pygm<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      rats (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05), contractions were evoked with prior infusion of lactate (pH 6.0) in an attempt to restore the effect of lactate and hydrogen ions. Contraction of freely perfused muscles increased blood lactate and decreased muscle pH in\n                      <jats:italic>pygm<\/jats:italic>\n                      <jats:sup>+\/+<\/jats:sup>\n                      rats only. Despite these differences, the reflex pressor and sympathetic responses to freely perfused contraction did not differ between groups (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.992). During ischaemia, contraction increased muscle lactate and hydrogen ion production in\n                      <jats:italic>pygm<\/jats:italic>\n                      <jats:sup>+\/+<\/jats:sup>\n                      rats (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0134), whereas it had no effect in\n                      <jats:italic>pygm<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      rats (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&gt;\u00a00.783). Likewise, ischaemia exaggerated the reflex pressor, and sympathetic responses to contraction in\n                      <jats:italic>pygm<\/jats:italic>\n                      <jats:sup>+\/+<\/jats:sup>\n                      but not in\n                      <jats:italic>pygm<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      rats. This exaggeration was restored when a solution of lactate (pH 6.0) was infused prior to the contraction in\n                      <jats:italic>pygm<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      rats. We conclude that lactate and hydrogen accumulation in contracting myocytes play a key role in evoking the metabolic component of the EPR during ischaemic but not during freely perfused contractions.\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\/tjp16058-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>Conflicting results exist about the role played by lactate and hydrogen ions in evoking the exercise pressor reflex.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Using CRISP\u2010Cas9, we rendered the myophosphorylase gene non\u2010functional to block the production of lactate and hydrogen ions. The exercise pressor reflex was evoked in decerebrated rats by statically contracting the triceps surae muscles with or without muscle ischaemia.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Static contraction elevated the concentration of lactate and hydrogen ions in\n                            <jats:italic>pygm<\/jats:italic>\n                            <jats:sup>+\/+<\/jats:sup>\n                            but not in\n                            <jats:italic>pygm<\/jats:italic>\n                            <jats:sup>\u2212\/\u2212<\/jats:sup>\n                            rats. Despite these differences, the exercise pressor reflex was not different between groups.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Acute muscle ischaemia exaggerated the concentration of lactate and hydrogen ions in\n                            <jats:italic>pygm<\/jats:italic>\n                            <jats:sup>+\/+<\/jats:sup>\n                            but not in\n                            <jats:italic>pygm<\/jats:italic>\n                            <jats:sup>\u2212\/\u2212<\/jats:sup>\n                            rats. Likewise, acute muscle ischaemia exaggerated the exercise pressor reflex in\n                            <jats:italic>pygm<\/jats:italic>\n                            <jats:sup>+\/+<\/jats:sup>\n                            but not in\n                            <jats:italic>pygm<\/jats:italic>\n                            <jats:sup>\u2212\/\u2212<\/jats:sup>\n                            rats.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We conclude that lactate and hydrogen play a key role in evoking the exercise pressor reflex during ischaemic but not during freely perfused contractions.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp286488","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T02:05:32Z","timestamp":1714442732000},"page":"5053-5070","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Lactate and hydrogen ions play a predominant role in evoking the exercise pressor reflex during ischaemic contractions but not during freely perfused contractions"],"prefix":"10.1113","volume":"603","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":"Mitochondrial, Oxidative Stress and Muscular Protection Laboratory (UR3072), Faculty of Medicine University of Strasbourg  Strasbourg 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