{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T07:24:23Z","timestamp":1767943463110,"version":"3.49.0"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Cerebral autoregulation is a vital homeostatic mechanism that protects the brain from hypertension\u2010induced injury by adjusting cerebrovascular tone to maintain stable cerebral blood flow (CBF). Neonates exposed to chronic hypoxia often exhibit impaired cerebral autoregulation though\u00a0underlying molecular mechanisms remain unclear. Here, we investigated whether L\u2010type calcium channels (LTCCs), known to be essential to the myogenic response in adults, also play a role in newborn cerebral autoregulation. We further examined whether chronic hypoxia impairs cerebral autoregulation in newborn lambs via LTCC\u2010dependent pathways. Using laser Doppler flowmetry to measure cerebral blood flow during graded acute hypertensive challenges, we demonstrated that normoxic lambs maintain both steady\u2010state (sustained control of blood flow over several minutes) and dynamic (rapid, beat\u2010to\u2010beat adjustments) autoregulation. By contrast, chronically hypoxic lambs exhibit pressure\u2010passive CBF responses, consistent with cerebral autoregulation compromise. Intravenous nifedipine, a selective LTCC blocker, abolished cerebral autoregulation in normoxic lambs, mimicking the hypoxic phenotype. Conversely, nifedipine had no additional effect in hypoxic lambs, suggesting pre\u2010existing LTCC suppression. Middle cerebral arteries isolated from hypoxic lambs exhibited reduced baseline tone and minimal responses to stretch or high\u2010potassium depolarization, even before nifedipine administration. These results confirm hypoxia\u2010induced loss of cerebral autoregulation via pathways involving LTCC function in neonatal cerebral arteries. Collectively, our findings establish that chronic hypoxia impairs neonatal cerebral autoregulation by attenuating LTCC\u2010mediated myogenic reactivity. This mechanism probably contributes to cerebral vulnerability in high\u2010risk neonates and represents a potential therapeutic target.\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\/tjp70221-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>Chronic hypoxia attenuates steady\u2010state cerebral autoregulation in newborn lambs, making cerebral blood flow pressure\u2010passive even after normoxia is restored.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Dynamic autoregulation is significantly blunted by chronic hypoxia, resembling the loss seen in normoxic lambs after L\u2010type calcium channel blockade.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>L\u2010type calcium channels are essential for neonatal autoregulation because nifedipine disrupts cerebral blood flow control in normoxic lambs but has little effect in hypoxic lambs.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Hypoxic arteries exhibit weak myogenic tone and a limited response to nifedipine, indicating that intrinsic L\u2010type calcium channel\u2010dependent pathway dysfunction contributes to the\n                            <jats:italic>in vivo<\/jats:italic>\n                            deficits.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp289790","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T04:17:27Z","timestamp":1762834647000},"page":"548-565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic hypoxia impairs L\u2010type Ca\n                    <sup>2+<\/sup>\n                    channel\u2010mediated myogenic vasoconstriction and cerebral autoregulation in newborn lambs"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3726-0854","authenticated-orcid":false,"given":"Stephen 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Pediatrics, Division of Neonatology Loma Linda University School of Medicine  Loma Linda CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9386-8938","authenticated-orcid":false,"given":"Lubo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lawrence D Longo, MD, Center for Perinatal Biology Loma Linda University School of Medicine  Loma Linda CA USA"},{"name":"Department of Basic Sciences, Divisions of Physiology, Pharmacology, and Biochemistry Loma Linda University School of Medicine Loma Linda CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5331-5677","authenticated-orcid":false,"given":"William J.","family":"Pearce","sequence":"additional","affiliation":[{"name":"Lawrence D Longo, MD, Center for Perinatal Biology Loma Linda University School of Medicine  Loma Linda CA USA"},{"name":"Department of Basic Sciences, Divisions of Physiology, Pharmacology, and 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