{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T22:58:16Z","timestamp":1774047496002,"version":"3.50.1"},"reference-count":84,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"Key points<\/jats:title>\nWe investigated the influence of arterial () with and without acute experimental metabolic alkalosis on neurovascular coupling (NVC).<\/jats:p><\/jats:list-item>\nWe assessed stepwise iso\u2010oxic alterations in prior to and following intravenous NaHCO3<\/jats:sub> to acutely elevate arterial pH and [HCO3<\/jats:sub>\u2013<\/jats:sup>].<\/jats:p><\/jats:list-item>\nThe NVC response was not altered following NaHCO3<\/jats:sub> between stepwise stages; therefore, NVC is acutely mediated by rather than the prevailing arterial [H+<\/jats:sup>]\/pH.<\/jats:p><\/jats:list-item>\nThe NVC response was attenuated by 27\u201338% with \u221210\u00a0mmHg and the absolute peak change was reduced by \u221219% with +10\u00a0mmHg irrespective of acutely elevated arterial pH\/[HCO3<\/jats:sub>\u2013<\/jats:sup>].<\/jats:p><\/jats:list-item>\nThe NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus<\/jats:italic> hypocapnia (24\u00a0\u00b1\u00a05 vs<\/jats:italic>. 7\u00a0\u00b1\u00a05\u00a0s, respectively) likely indicating an influence of resting cerebrovascular tone on NVC responsiveness.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>Abstract<\/jats:title>Elevations in cerebral metabolism necessitate appropriate coordinated and localized increases in cerebral blood flow (i.e. neurovascular coupling; NVC). Recent pre\u2010clinical work indicates that arterial () mediates NVC independently of arterial\/extracellular pH; this has yet to be experimentally tested in humans. The goal of this study was to investigate the hypotheses that: (1) the NVC response would be unaffected by acute experimentally elevated arterial pH; rather, would regulate any changes in NVC; and (2) stepwise respiratory alkalosis and acidosis would each progressively reduce the NVC response. Ten healthy males completed a standardized visual stimulus\u2010evoked NVC test during matched stepwise iso\u2010oxic alterations in (hypocapnia: \u22125, \u221210\u00a0mmHg; hypercapnia: +5, +10\u00a0mmHg) prior to and following intravenous NaHCO3<\/jats:sub> (8.4%, 50\u00a0mEq\/50\u00a0ml) that elevated arterial pH (7.406\u00a0\u00b1\u00a00.019 vs<\/jats:italic>. 7.457\u00a0\u00b1\u00a00.029; P<\/jats:italic>\u00a0<\u00a00.001) and [HCO3<\/jats:sub>\u2013<\/jats:sup>] (26.2\u00a0\u00b1\u00a01.5 vs<\/jats:italic>. 29.3\u00a0\u00b1\u00a00.9\u00a0mEq\/l; P<\/jats:italic>\u00a0<\u00a00.001). Although the NVC response was collectively attenuated by 27\u201338% with \u221210\u00a0mmHg (stage post hoc<\/jats:italic>: all P<\/jats:italic>\u00a0<\u00a00.05), this response was unaltered following NaHCO3<\/jats:sub> (all P\u00a0<\/jats:italic>>\u00a00.05) irrespective of the higher pH (P<\/jats:italic>\u00a0=\u00a00.002) at each matched stage of (P<\/jats:italic>\u00a0=\u00a00.417). The absolute peak change was reduced by \u221219 \u00b1\u00a041% with +10\u00a0mmHg irrespective of acutely elevated arterial pH\/[HCO3<\/jats:sub>\u2013<\/jats:sup>] (stage post hoc<\/jats:italic>: P<\/jats:italic>\u00a0=\u00a00.022). The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus<\/jats:italic> hypocapnia (24\u00a0\u00b1\u00a05 vs<\/jats:italic>. 7\u00a0\u00b1\u00a05\u00a0s, respectively; stage effect: P<\/jats:italic>\u00a0<\u00a00.001). Overall, these findings indicate that temporal patterns in NVC are acutely regulated by rather than arterial pH per se<\/jats:italic> in the setting of acute metabolic alkalosis in humans.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp281615","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T17:54:51Z","timestamp":1623261291000},"page":"3663-3676","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Alterations in arterial CO2<\/sub> rather than pH affect the kinetics of neurovascular coupling in humans"],"prefix":"10.1113","volume":"599","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6072-7277","authenticated-orcid":false,"given":"Hannah G.","family":"Caldwell","sequence":"first","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health School of Health and Exercise Sciences University of British Columbia Okanagan Kelowna BC V1V 1V7 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