{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:12:43Z","timestamp":1789776763886,"version":"4.0.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Phenylephrine is an alpha 1\u2010adrenergic receptor (\u03b11R) agonist. Evidence indicates activation of \u03b11Rs can initiate both vasoconstrictor and dilator signaling. How phenylephrine affects cerebrovascular regulation remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p xml:lang=\"en\">A retrospective analysis of data examining cerebral perfusion and blood pressure during systemic phenylephrine infusion in humans and swine was completed. Follow\u2010up experiments examining cerebral hemodynamics during intracarotid arterial infusion of phenylephrine in anesthetized swine were performed. Ex\u00a0vivo experiments were conducted on isolated porcine cerebral arteries.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Systemic phenylephrine infusion increased indices of cerebrovascular resistance in both humans (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.0423) and swine (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              &lt;0.0001) but did not decrease perfusion. Intracarotid phenylephrine infusion did not alter cerebrovascular resistance, but increased perfusion in control conditions (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.0045), whereas resistance increased (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              \u22640.0155) without altered perfusion during NOS (nitric oxide synthase) inhibition conditions. \u03b11Rs were detected on both extraluminal and intraluminal aspects of cerebral arteries, reflecting a population of vascular smooth muscle and endothelial \u03b11Rs, respectively. Extraluminal phenylephrine caused vasoconstriction whereas intraluminal phenylephrine elicited an endothelium\u2010dependent NO\u2010mediated dilation. NOS inhibition enhanced phenylephrine\u2010induced vasoconstriction in third\u2010order branch of the middle cerebral artery, but not the first\u2010order or second\u2010order pial arteries (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.0267), and this corresponded with an increased ratio of phosphorylated to total endothelial NOS protein content in third\u2010order versus first\u2010order and second\u2010order arteries (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              \u22640.0022). Phenylephrine\u2010induced constriction was greatest in first\u2010order arteries (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.0419), and this corresponded with increased perivascular adrenergic innervation and \u03b11R protein content in first\u2010order versus second\u2010order and third\u2010order arteries (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              \u22640.0054).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Neither systemic nor intracarotid phenylephrine infusion compromised cerebral perfusion, possibly related to increased endothelial NO signaling and reduced \u03b11R density in downstream pial arteries.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.125.042396","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T12:10:05Z","timestamp":1758802205000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of Phenylephrine on Cerebrovascular Regulation: A Translational Perspective"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0201-0528","authenticated-orcid":false,"given":"Adam M. S.","family":"Luchkanych","sequence":"first","affiliation":[{"name":"University of Saskatchewan","place":["Saskatoon, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breanna","family":"Barlage","sequence":"additional","affiliation":[{"name":"University of Saskatchewan","place":["Saskatoon, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Delgado","sequence":"additional","affiliation":[{"name":"University of Saskatchewan","place":["Saskatoon, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7572-7041","authenticated-orcid":false,"given":"Jude S.","family":"Morton","sequence":"additional","affiliation":[{"name":"University of Saskatchewan","place":["Saskatoon, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7120-0745","authenticated-orcid":false,"given":"Cameron J.","family":"Morse","sequence":"additional","affiliation":[{"name":"University of Saskatchewan","place":["Saskatoon, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8103-3485","authenticated-orcid":false,"given":"Erika M.","family":"Boerman","sequence":"additional","affiliation":[{"name":"University of Missouri","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5657-0059","authenticated-orcid":false,"given":"Ryan L.","family":"Hoiland","sequence":"additional","affiliation":[{"name":"University of British Columbia","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4487-301X","authenticated-orcid":false,"given":"Mypinder S.","family":"Sekhon","sequence":"additional","affiliation":[{"name":"University of British Columbia","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Tymko","sequence":"additional","affiliation":[{"name":"University of Guelph","place":["Guelph, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7944-4936","authenticated-orcid":false,"given":"Jaume","family":"Padilla","sequence":"additional","affiliation":[{"name":"University of Missouri","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1251-591X","authenticated-orcid":false,"given":"Craig A.","family":"Emter","sequence":"additional","affiliation":[{"name":"University of Missouri","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8182-6466","authenticated-orcid":false,"given":"Corey R.","family":"Tomczak","sequence":"additional","affiliation":[{"name":"University of Saskatchewan","place":["Saskatoon, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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