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We propose that curcumin prevents the development of hypertension by regulating AT<jats:sub>1<\/jats:sub> receptor (AT<jats:sub>1<\/jats:sub>R) expression in arteries. The present study examined how curcumin regulates AT<jats:sub>1<\/jats:sub>R expression in vascular smooth muscle cells and investigated the physiological significance of this regulation in angiotensin (Ang) II-induced hypertension. The results showed that curcumin decreased AT<jats:sub>1<\/jats:sub>R expression in a concentration- and time-dependent manner in vascular smooth muscle cells. Using luciferase reporters with an entire AT<jats:sub>1<\/jats:sub> or a mutant AT<jats:sub>1<\/jats:sub>R in A10 cells, the AT<jats:sub>1<\/jats:sub>R promoter activity was inhibited by 10<jats:sup>\u22126<\/jats:sup>M curcumin, and the proximal element (from \u221261 to +25\u2009bp) of the AT<jats:sub>1<\/jats:sub>R promoter was crucial for curcumin-induced AT<jats:sub>1<\/jats:sub>R down-regulation. An electrophoretic mobility shift assay showed that curcumin decreased specificity protein 1 (SP1) binding with the AT<jats:sub>1<\/jats:sub>R promoter in A10 cells. Curcumin treatment reduced Ang II-induced hypertension in C57Bl\/6J mice, which was accompanied by lower AT<jats:sub>1<\/jats:sub>R expression in the arteries and decreased Ang II-mediated vasoconstriction in the mesenteric artery. These findings indicate that curcumin down-regulates AT<jats:sub>1<\/jats:sub>R expression in A10 cells by affecting SP1\/AT<jats:sub>1<\/jats:sub>R DNA binding, thus reducing AT<jats:sub>1<\/jats:sub>R-mediated vasoconstriction and subsequently prevents the development of hypertension in an Ang II-induced hypertensive model.<\/jats:p>","DOI":"10.1038\/srep25579","type":"journal-article","created":{"date-parts":[[2016,5,5]],"date-time":"2016-05-05T09:49:17Z","timestamp":1462441757000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Curcumin Exerts its Anti-hypertensive Effect by Down-regulating the AT1 Receptor in Vascular Smooth Muscle Cells"],"prefix":"10.1038","volume":"6","author":[{"given":"Yonggang","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Eric","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,5]]},"reference":[{"key":"BFsrep25579_CR1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.5049\/EBP.2013.11.2.41","volume":"11","author":"JY Moon","year":"2013","unstructured":"Moon, J. 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