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Apelin mRNA and protein levels were detected with real-time RT-PCR and Western blots, respectively. Expression of apelin was significantly enhanced in the RVLM of spontaneously hypertensive rat (SHR) compared with normotensive Wistar\u2013Kyoto (WKY) rats. To study the functional consequence of upregulated apelin expression, apelin was overexpressed by bilateral microinjection of the AAV2-apelin viral vector into the RVLM of WKY rats. Immunofluorescence staining and Western blots demonstrated that microinjection of AAV2-apelin into the RVLM resulted in a significant increase in apelin expression, which was associated with a chronic elevation in blood pressure and cardiac hypertrophy. In addition, direct microinjection of exogenous apelin-13 (200 pmol in 50 nL) into the RVLM caused a 20 mm Hg elevation in blood pressure and a 24% increase in sympathetic nerve activity. The present study is the first to show that apelin expression is enhanced in the RVLM of SHR versus WKY rats and that overexpression of this gene in the RVLM results in chronic blood pressure elevation and cardiac hypertrophy in normotensive rats. Thus, the apelin system in the RVLM may play a very important role in central blood pressure regulation and in the pathogenesis of hypertension.<\/jats:p>","DOI":"10.1161\/circresaha.108.192302","type":"journal-article","created":{"date-parts":[[2009,5,15]],"date-time":"2009-05-15T02:19:52Z","timestamp":1242353992000},"page":"1421-1428","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":74,"title":["Apelin Gene Transfer Into the Rostral Ventrolateral Medulla Induces Chronic Blood Pressure Elevation in Normotensive Rats"],"prefix":"10.1161","volume":"104","author":[{"given":"Qi","family":"Zhang","sequence":"first","affiliation":[{"name":"From the Department of Pharmaceutical Sciences (Q.Z., F.Y., S.T.O, C.S.), College of Pharmacy, North Dakota State University, Fargo; Department of Physiology and Functional Genomics (M.K.R.), College of Medicine, University of Florida, Gainesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanrong","family":"Yao","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutical Sciences (Q.Z., F.Y., S.T.O, C.S.), College of Pharmacy, North Dakota State University, Fargo; Department of Physiology and Functional Genomics (M.K.R.), College of Medicine, University of Florida, Gainesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohan K.","family":"Raizada","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutical Sciences (Q.Z., F.Y., S.T.O, C.S.), College of Pharmacy, North Dakota State University, Fargo; Department of Physiology and Functional Genomics (M.K.R.), College of Medicine, University of Florida, Gainesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen T.","family":"O'Rourke","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutical Sciences (Q.Z., F.Y., S.T.O, C.S.), College of Pharmacy, North Dakota State University, Fargo; Department of Physiology and Functional Genomics (M.K.R.), College of Medicine, University of Florida, Gainesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengwen","family":"Sun","sequence":"additional","affiliation":[{"name":"From the Department of Pharmaceutical Sciences (Q.Z., F.Y., S.T.O, C.S.), College of Pharmacy, North Dakota State University, Fargo; Department of Physiology and Functional Genomics (M.K.R.), College of Medicine, University of Florida, Gainesville."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9489"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0740034.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(93)90495-O"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0359"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(03)01821-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00320.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2004.09.018"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(01)00236-1"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2004.07.033"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06804"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2007.04.002"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm005"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1159\/000054609"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(00)00072-5"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00192-6"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(95)00026-8"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.2003.01070.x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2002.03640.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2002.03665.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.38.3.549"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(00)00225-9"},{"key":"e_1_3_3_22_2","first-page":"II15","volume":"19","year":"2000","unstructured":"Mancia G, Grassi G, Parati G, Zanchetti A. 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