{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T22:27:46Z","timestamp":1778106466997,"version":"3.51.4"},"reference-count":63,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/501100000037","name":"Gouvernement du Canada | CIHR | Institute of Health Services and Policy Research (IHSPR)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000037","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000145","name":"Alberta Innovates - Health Solutions (AIHS)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000145","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SIDS Calgary"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:p>The stress peptide pituitary adenylate cyclase activating polypeptide (PACAP) and its specific receptor PACAP type 1 receptor (PAC1) have been implicated in sudden infant death syndrome (SIDS). PACAP is also critical to the neonatal cardiorespiratory response to homeostatic stressors identified in SIDS, including hypoxia. However, which of PACAP\u2019s three receptors, PAC1, vasoactive intestinal peptide receptor type 1 (VPAC1), and\/or vasoactive intestinal peptide receptor type 2 (VPAC2), are involved is unknown. In this study, we hypothesized that PAC1, but not VPAC2, is involved in mediating the cardiorespiratory response to hypoxia during neonatal development. To test this hypothesis, head-out plethysmography and surface ECG electrodes were used to assess the cardiorespiratory variables of unanesthetized postnatal day 4 PAC1 and VPAC2-knockout (KO) and wild-type (WT) mice in response to a 10% hypoxic challenge. Our results demonstrate that compared with WT pups, the early and late hypoxic rate of expired CO<jats:sub>2<\/jats:sub>(V\u0307co<jats:sub>2<\/jats:sub>), V\u0307co<jats:sub>2<\/jats:sub>and ventilatory responses were blunted in PAC1-KO neonates, and during the posthypoxic period, minute ventilation (V\u0307e), V\u0307co<jats:sub>2<\/jats:sub>and heart rate were increased, while the increase in apneas normally associated with the posthypoxic period was reduced. Consistent with impaired cardiorespiratory control in these animals, the V\u0307e\/V\u0307co<jats:sub>2<\/jats:sub>slope was reduced in PAC1-KO pups, suggesting that breathing was inappropriately matched to metabolism. In contrast, VPAC2-KO pups exhibited elevated heart rate variability during hypoxia compared with WT littermates, but the effects of the VPAC2-KO genotype on breathing were minimal. These findings suggest that PAC1 plays the principal role in mediating the cardiorespiratory effects of PACAP in response to hypoxic stress during neonatal development and that defective PACAP signaling via PAC1 may contribute to the pathogenesis of SIDS.<\/jats:p>","DOI":"10.1152\/ajpregu.00250.2018","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T18:55:18Z","timestamp":1550084118000},"page":"R594-R606","source":"Crossref","is-referenced-by-count":10,"title":["Impaired neonatal cardiorespiratory responses to hypoxia in mice lacking PAC1 or VPAC2 receptors"],"prefix":"10.1152","volume":"316","author":[{"given":"Karlene T.","family":"Barrett","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3824-9293","authenticated-orcid":false,"given":"Shabih U.","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morris H.","family":"Scantlebury","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinical Neuroscience, Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J. 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