{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:58:01Z","timestamp":1781528281232,"version":"3.54.1"},"reference-count":72,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      ATP acting on P2X3 receptors contributes to carotid body (CB) hyperexcitability in spontaneously hypertensive rats (SHRs). We investigated whether this reflects altered ATP release and\/or impaired ATP metabolism. Using\n                      <jats:italic>in vitro<\/jats:italic>\n                      CB preparations, we quantified ATP release in Wistar rats and SHRs (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a010 each) and found significantly greater ATP release in SHRs (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.00062). Intracellular ATP depletion in dissociated glomus cells was similar between strains (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a04 each). Morphometric analysis revealed a disproportionate increase in glomus tissue, measured as tyrosine hydroxylase\u2010positive area, in juvenile SHRs compared with Wistar rats (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a08 each;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a05.44 \u00d7 10\n                      <jats:sup>\u2212<\/jats:sup>\n                      <jats:sup>6<\/jats:sup>\n                      ). This enlargement was associated with upregulated\n                      <jats:italic>Epas1<\/jats:italic>\n                      mRNA (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a08 each), encoding HIF\u20112\u03b1, a driver of CB hyperplasia. Transcripts for ATP\u2011degrading enzymes Enpp1, Enpp3 and Entpd2 were also downregulated in SHRs (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a08 each), suggesting reduced extracellular ATP breakdown. Electrophysiological recordings\n                      <jats:italic>in vitro<\/jats:italic>\n                      and reflex testing\n                      <jats:italic>in situ<\/jats:italic>\n                      showed that topical ATP or \u03b1,\u03b2\u2011methylene\u2010ATP applied to the CB evoked tachypnoea and sympathoexcitation in both strains, but SHRs displayed a greater sympathetic reflex (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a04 each;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.037), indicating increased sensitivity to purinergic stimulation. In contrast, testing adenosine transmission revealed no difference between strains; adenosine did not contribute to CB hyperexcitability in SHRs (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a011 each;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.53). Overall, increased ATP release in SHRs likely reflects CB enlargement from glomus cell expansion, compounded by reduced ATP\u2011degrading enzyme expression, thereby enhancing purinergic drive and chemoreflex sensitivity.\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\/tjp70536-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>The carotid bodies (CBs) of spontaneously hypertensive rats (SHRs) release more ATP than those of Wistar rats.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Glomus cell expansion underpins CB hyperplasia and contributes to increased ATP release in juvenile SHRs.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Upregulated\n                            <jats:italic>Epas1<\/jats:italic>\n                            (i.e. HIF\u20102\u03b1) gene expression is likely responsible for CB hyperplasia in SHRs.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>ATP transmission is linked to exacerbated chemoreflex sympathoexcitation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Adenosine transmission does not contribute to CB hyperexcitability in SHRs.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp288931","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T01:22:52Z","timestamp":1776648172000},"page":"4678-4706","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exacerbated ATP transmission in the carotid body is linked to glomus cell expansion in spontaneously hypertensive rats"],"prefix":"10.1113","volume":"604","author":[{"given":"Igor S. 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