{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:24:04Z","timestamp":1788488644127,"version":"build-2803163510"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2019.01548","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T09:17:42Z","timestamp":1579684662000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Kang Le Xin Reduces Blood Pressure Through Inducing Endothelial-Dependent Vasodilation by Activating the AMPK-eNOS Pathway"],"prefix":"10.3389","volume":"10","author":[{"given":"Yixiu","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuxin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangfei","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weina","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Aruhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiqiang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baofeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,1,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/598271","article-title":"Endothelial dysfunction in experimental models of arterial hypertension: cause or consequence","volume":"2014","author":"Bernatova","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"B2","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1124\/pr.115.010652","article-title":"Mechanisms of vascular smooth muscle contraction and the basis for pharmacologic treatment of smooth muscle disorders","volume":"68","author":"Brozovich","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/s0165-6147(02)02050-3","article-title":"EDHF: bringing the concepts together","volume":"23","author":"Busse","year":"2002","journal-title":"Trends Pharmacol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1161\/HYPERTENSIONAHA.113.02026","article-title":"Refractory hypertension: determination of prevalence, risk factors and comorbidities in a large, population-based cohort","volume":"63","author":"Calhoun","year":"2016","journal-title":"Hypertension"},{"key":"B5","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.vph.2008.06.008","article-title":"Endothelial nitric oxide and its pathophysiologic regulation","volume":"49","author":"Chatterjee","year":"2008","journal-title":"Vasc. Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1152\/physrev.000472009","article-title":"Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives","volume":"91","author":"Chiu","year":"2013","journal-title":"Physiol. Rev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1161\/01.str.0000437068.30550.cf","article-title":"Factors influencing the decline in stroke mortality: a statement from the American Heart Association\/American Stroke Association","volume":"45","author":"Daniel","year":"2014","journal-title":"Stroke"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1111\/j.1476-5381.2010.00817.x","article-title":"Acute activation of eNOS by stains involves scavenger receptor-B1, G protein submit Gi, phospholipase C and calcium influx","volume":"160","author":"Datar","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1146\/annurev.pharmtox.44.101802.121844","article-title":"The regulation and pharmacology of endothelial nitric oxide synthase","volume":"46","author":"Dudzinski","year":"2006","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e146","DOI":"10.1161\/CIR.0000000000000485","article-title":"Heart disease and stroke statistics\u20142017 Update: a report from the American Heart Association","volume":"135","author":"Emelia","year":"2017","journal-title":"Circulation"},{"key":"B11","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1113\/jphysiol.1997.sp021852","article-title":"Intestinal blood flow is controlled by both feed arteries and microcirculatory resistance vessels in freely moving rats","volume":"498","author":"Fenger-Gron","year":"1997","journal-title":"J. Physiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1111\/j.1751-7176.2012.00606.x","article-title":"Impaired vasodilation in the pathogenesis of hypertension: focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins","volume":"14","author":"Giles","year":"2012","journal-title":"J. Clin. Hypertens."},{"key":"B13","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1161\/CIRCRESAHA.115.306301","article-title":"Endothelial cell dysfunction and the pathobiology of atherosclerosis","volume":"118","author":"Gimbrone","year":"2016","journal-title":"Circ. Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"F193","DOI":"10.1152\/ajprenal.2001.280.2.F193","article-title":"Cellular regulation of endothelial nitric oxide synthase","volume":"280","author":"Govers","year":"2001","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1111\/1440-1681.12550","article-title":"Aliskiren improves endothelium-dependent relaxation of thoracic aorta by activating PI3K\/Akt\/eNOS signal pathway in SHR","volume":"43","author":"Gu","year":"2016","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/377239a0","article-title":"Hypertension in mice lacking the gene for endothelial nitric oxide synthase","volume":"377","author":"Huang","year":"1995","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1089\/wound.2013.0517","article-title":"Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair","volume":"3","author":"Johnson","year":"2014","journal-title":"Adv. Wound Care (New Rochelle)"},{"key":"B18","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/jhh.2013.140","article-title":"Apparent and true resistant hypertension: definition, prevalence and outcomes","volume":"28","author":"Judd","year":"2014","journal-title":"J. Hum. Hypertens."},{"key":"B19","doi-asserted-by":"publisher","first-page":"141","DOI":"10.5487\/TR.2014.30.3.141","article-title":"Endothelium-derived relaxing factors of small resistance arteries in hypertension","volume":"30","author":"Kang","year":"2014","journal-title":"Toxicol. Res."},{"key":"B20","first-page":"469","article-title":"Prostacyclin increases cAMP in coronary arteries","volume":"5","author":"Kukovetz","year":"1979","journal-title":"J. Cyclic. Nucleotide Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.jphs.2015.05.006","article-title":"Aurantio-obtusin relaxes systemic arteries through endothelial PI3K\/AKT\/eNOS-dependent signaling pathway in rats","volume":"128","author":"Li","year":"2015","journal-title":"J. Pharm. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"4300","DOI":"10.1111\/bph.12804","article-title":"Emodin inhibits tonic tension through suppressing PKC\u03b4-mediated inhibition of myosin phosphatase in rat isolated thoracic aorta","volume":"171","author":"Lim","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1093\/eurheartj\/ehw303","article-title":"Interventional procedures and future drug therapy for hypertension","volume":"38","author":"Lobo","year":"2017","journal-title":"Eur. Heart J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1161\/HYPERTENSIONAHA.114.04683","article-title":"Brainstem hypoxia contributes to the development of hypertension in the spontaneously hypertensive rat","volume":"65","author":"Marina","year":"2015","journal-title":"Hypertension"},{"key":"B24","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1161\/CIRCULATIONAHA.115.018912","article-title":"Global disparities of hypertension prevalence and control: A systematic analysis of population-based studies from 90 countries","volume":"134","author":"Mills","year":"2016","journal-title":"Circulation"},{"key":"B26","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.yjmcc.2006.05.023","article-title":"Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation","volume":"42","author":"Mount","year":"2007","journal-title":"J. Mol. Cell Cardiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e63","DOI":"10.5114\/amsad.2019.84539","article-title":"Prevalence of endothelial nitric oxide synthase (ENOS) gene G894T polymorphism and its association with hypertension: a population-based study with Brazilian women","volume":"18","author":"Neto","year":"2019","journal-title":"Arch. Med. Sci. Atheroscler. Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.vph.2013.07.001","article-title":"Propiony-L-carnitine induces eNOS activation and nitric oxide syntheis endothelial cells via PI3K and Akt kinases","volume":"59","author":"Ning","year":"2013","journal-title":"Vasc. Pharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/hr.2014.169","article-title":"Systolic hypertension: an increasing clinical challenge in Asia","volume":"38","author":"Park","year":"2015","journal-title":"Hypertens. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.7150\/ijbs.7502","article-title":"The vascular endothelium and human diseases","volume":"9","author":"Rajendran","year":"2013","journal-title":"Int. J. Biol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1002\/jcb.240460106","article-title":"Endothelium-derived relaxing and contracting factors","volume":"46","author":"Rubanvi","year":"1991","journal-title":"J. Cell Biochem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1186\/s12916-019-1313-x","article-title":"Comparative risk of renal, cardiovascular, and mortality outcomes in controlled, uncontrolled resistant, and non-resistant hypertension","volume":"88","author":"Sim","year":"2015","journal-title":"Kidney Int."},{"key":"B33","doi-asserted-by":"publisher","first-page":"H344","DOI":"10.1152\/ajpheart.00952.2012","article-title":"Suppression of endoplasmic reticulum stress improves endothelium-dependent contractile responses in aorta of the spontaneously hypertensive rat","volume":"305","author":"Spitler","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B34","first-page":"333","article-title":"Role of nitric oxide and other endothelium-derived factors","volume":"39","author":"Stankevicius","year":"2003","journal-title":"Medicina"},{"key":"B35","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1007\/s00424-010-0786-4","article-title":"Endothelial dysfunction: A strategic target in the treatment of hypertension","volume":"459","author":"Tang","year":"2010","journal-title":"Pfulugers. Arch."},{"key":"B36","doi-asserted-by":"publisher","first-page":"H1698","DOI":"10.1152\/ajpheart.00377.2013","article-title":"Role of 20-HETE, TRPC channels, and BKCa in dysregulation of pressure-induced Ca2+ signaling and myogenic constriction of cerebral arteries in aged hypertensive mice","volume":"305","author":"Toth","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1093\/cvr\/cvy023","article-title":"Vascular smooth muscle contraction in hypertension","volume":"114","author":"Touyz","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/s0008-6363(00)00172-3","article-title":"Calcium signaling in endothelial cells","volume":"48","author":"Tran","year":"2000","journal-title":"Cardiovasc. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1002\/cphy.c160011","article-title":"Smooth muscle ion channels and regulation of vascular tone in resistance arteries and arterioles","volume":"7","author":"Tykocki","year":"2018","journal-title":"Compr. Physiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1161\/ATVBAHA.112.301068","article-title":"Circulating blood eNOS contributes to the regulation of systemic blood pressure and nitrite homeostasis","volume":"33","author":"Wood","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.3109\/10715762.2012.715369","article-title":"Nitric oxide (NO) generation but not ROS plays a major role in silibinin-induced autophagic and apoptotic death in human epidermoid carcinoma A431 cells","volume":"46","author":"Yu","year":"2012","journal-title":"Free Radic. Res."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149386","article-title":"Jujuboside B reduces vascular tension by increasing Ca2+ influx and activating endothelial nitric oxide synthase","volume":"11","author":"Zhao","year":"2016","journal-title":"PloS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"32552","DOI":"10.1074\/jbc.M204512200","article-title":"Modulation by peroxynitrite of Akt- and AMP-activated kinase-dependent Ser1179 phosphorylation of endothelial nitric oxide synthase","volume":"277","author":"Zou","year":"2002","journal-title":"J. Biol. Chem."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.01548\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T09:17:44Z","timestamp":1579684664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.01548\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,22]]},"references-count":43,"alternative-id":["10.3389\/fphar.2019.01548"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2019.01548","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,22]]},"article-number":"1548"}}