{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:16:41Z","timestamp":1793060201308,"version":"4.5.0"},"reference-count":76,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,12,26]],"date-time":"2016-12-26T00:00:00Z","timestamp":1482710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL\u2010073965"],"award-info":[{"award-number":["HL\u2010073965"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL\u2010083298"],"award-info":[{"award-number":["HL\u2010083298"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 DK080674"],"award-info":[{"award-number":["T32 DK080674"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Endothelial inwardly rectifying K<jats:sup>+<\/jats:sup> (Kir2.1) channels regulate flow\u2010induced vasodilatation via nitric oxide (NO) in mouse mesenteric resistance arteries.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Deficiency of Kir2.1 channels results in elevated blood pressure and increased vascular resistance.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Flow\u2010induced vasodilatation in human resistance arteries is also regulated by inwardly rectifying K<jats:sup>+<\/jats:sup> channels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study presents the first direct evidence that Kir channels play a critical role in physiological endothelial responses to flow.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Inwardly rectifying K<jats:sup>+<\/jats:sup> (Kir) channels are known to be sensitive to flow, but their role in flow\u2010induced endothelial responses is not known. The goal of this study is to establish the role of Kir channels in flow\u2010induced vasodilatation and to provide first insights into the mechanisms responsible for Kir signalling in this process. First, we establish that primary endothelial cells isolated from murine mesenteric arteries express functional Kir2.1 channels sensitive to shear stress. Then, using the Kir2.1<jats:sup>+\/\u2212<\/jats:sup> heterozygous mouse model, we establish that downregulation of Kir2.1 results in significant decrease in shear\u2010activated Kir currents and inhibition of endothelium\u2010dependent flow\u2010induced vasodilatation (FIV) assayed in pressurized mesenteric arteries pre\u2010constricted with endothelin\u20101. Deficiency in Kir2.1 also results in the loss of flow\u2010induced phosphorylation of eNOS and Akt, as well as inhibition of NO generation. All the effects are fully rescued by endothelial cell (EC)\u2010specific overexpression of Kir2.1. A component of FIV that is Kir independent is abrogated by blocking Ca<jats:sup>2+<\/jats:sup>\u2010sensitive K<jats:sup>+<\/jats:sup> channels. Kir2.1 has no effect on endothelium\u2010independent and K<jats:sup>+<\/jats:sup>\u2010induced vasodilatation in denuded arteries. Kir2.1<jats:sup>+\/\u2212<\/jats:sup> mice also show increased mean blood pressure measured by carotid artery cannulation and increased microvascular resistance measured using a tail\u2010cuff. Importantly, blocking Kir channels also inhibits flow\u2010induced vasodilatation in human subcutaneous adipose microvessels. Endothelial Kir channels contribute to FIV of mouse mesenteric arteries via an NO\u2010dependent mechanism, whereas Ca<jats:sup>2+<\/jats:sup>\u2010sensitive K<jats:sup>+<\/jats:sup> channels mediate FIV via an NO\u2010independent pathway. Kir2 channels also regulate vascular resistance and blood pressure. Finally, Kir channels also contribute to FIV in human subcutaneous microvessels.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp273255","type":"journal-article","created":{"date-parts":[[2016,11,17]],"date-time":"2016-11-17T11:23:42Z","timestamp":1479381822000},"page":"2339-2364","source":"Crossref","is-referenced-by-count":110,"title":["Inwardly rectifying K<sup>+<\/sup> channels are major contributors to flow\u2010induced vasodilatation in resistance arteries"],"prefix":"10.1113","volume":"595","author":[{"given":"Sang Joon","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy University of Illinois at Chicago  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibra S.","family":"Fancher","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy University of Illinois at Chicago  Chicago IL 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