{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:30:23Z","timestamp":1783675823464,"version":"3.55.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2014,7]]},"abstract":"\n Objective\u2014<\/jats:title>\n Vascular endothelium plays an important role to maintain cardiovascular homeostasis through several mechanisms, including endothelium-dependent hyperpolarization (EDH). We have recently demonstrated that EDH is involved in endothelial metabolic regulation in mice. However, it remains to be examined whether AMP-activated protein kinase (AMPK), an important metabolic regulator, is involved in EDH and if so, whether endothelial AMPK (eAMPK) plays a role for circulatory regulation.<\/jats:p>\n <\/jats:sec>\n \n Approach and Results\u2014<\/jats:title>\n \n We examined the role of eAMPK in EDH, using mice with endothelium-specific deficiency of \u03b1-catalytic subunit of AMPK, either \u03b1\n 1<\/jats:sub>\n (eAMPK\u03b1\n 1<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n \u03b1\n 2<\/jats:sub>\n +\/+<\/jats:sup>\n ) or \u03b1\n 2<\/jats:sub>\n (eAMPK\u03b1\n 1<\/jats:sub>\n +\/+<\/jats:sup>\n \u03b1\n 2<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n ) alone or both of them (eAMPK\u03b1\n 1<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n \u03b1\n 2<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n ). We performed telemetry, organ chamber, electrophysiological, and Langendorff experiments to examine blood pressure, vascular responses, hyperpolarization of membrane potential, and coronary flow responses, respectively. Hypertension was noted throughout the day in eAMPK\u03b1\n 1<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n \u03b1\n 2<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n and eAMPK\u03b1\n 1<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n \u03b1\n 2<\/jats:sub>\n +\/+<\/jats:sup>\n but not in eAMPK\u03b1\n 1<\/jats:sub>\n +\/+<\/jats:sup>\n \u03b1\n 2<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n mice when compared with respective control. Importantly, endothelium-dependent relaxations, EDH, and coronary flow increase were all significantly reduced in eAMPK\u03b1\n 1<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n \u03b1\n 2<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n and eAMPK\u03b1\n 1<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n \u03b1\n 2<\/jats:sub>\n +\/+<\/jats:sup>\n but not in eAMPK\u03b1\n 1<\/jats:sub>\n +\/+<\/jats:sup>\n \u03b1\n 2<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n mice. In contrast, endothelium-independent relaxations to sodium nitroprusside (a NO donor), NS-1619 (a Ca\n 2+<\/jats:sup>\n -activated K\n +<\/jats:sup>\n channel opener), and exogenous H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n were almost comparable among the groups. In eAMPK\u03b1\n 1<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n \u03b1\n 2<\/jats:sub>\n \u2212\/\u2212<\/jats:sup>\n mice, antihypertensive treatment with hydralazine or long-term treatment with metformin (a stimulator of AMPK) failed to restore EDH-mediated responses.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions\u2014<\/jats:title>\n \n These results provide the first direct evidence that \u03b1\n 1<\/jats:sub>\n subunit of eAMPK substantially mediates EDH responses of microvessels and regulates blood pressure and coronary flow responses in mice in vivo, demonstrating the novel role of eAMPK in cardiovascular homeostasis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/atvbaha.114.303735","type":"journal-article","created":{"date-parts":[[2014,5,23]],"date-time":"2014-05-23T08:06:01Z","timestamp":1400832361000},"page":"1505-1513","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":67,"title":["Endothelial AMP-Activated Protein Kinase Regulates Blood Pressure and Coronary Flow Responses Through Hyperpolarization Mechanism in Mice"],"prefix":"10.1161","volume":"34","author":[{"given":"Budbazar","family":"Enkhjargal","sequence":"first","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Godo","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayuko","family":"Sawada","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nergui","family":"Suvd","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Saito","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Noda","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimio","family":"Satoh","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Shimokawa","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/288373a0"},{"key":"e_1_3_5_3_2","first-page":"66","article-title":"The role of prostacyclin in vascular tissue.","volume":"38","author":"Moncada S","year":"1979","unstructured":"Moncada S, Vane JR. 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