{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:26:02Z","timestamp":1791321962649,"version":"4.3.1"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1999,3]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014The aim of the present study was to analyze whether the cardiac endothelin system contributes to cardiac remodeling in rats with 2-kidney, 1 clip (2K1C) renovascular hypertension. The endothelin system seems to be a promising candidate for cardiac remodeling because endothelin (ET)-1 promotes growth of cardiomyocytes in vitro and induces cardiac collagen synthesis. The activity of the cardiac endothelin system was analyzed by measuring cardiac tissue big ET-1 and ET-1 concentrations as well as by estimating the cardiac expression of the ETA and ETB receptors 10 days, 4 weeks, and 12 weeks after the renal artery was clipped. The effects of long-term treatment with ETA, ETB, and combined ETA\/ETB receptor antagonists on cardiac hypertrophy, media\/lumen ratio of intracardiac arteries, and left ventricular fibrosis were also analyzed. This study demonstrated that the overall left ventricular cardiac endothelin system has a similar activity in the early, middle, and late stages of 2K1C renovascular hypertension compared with sham-operated controls. Fibrosis of the left ventricle and hypertrophy of intracardiac arteries, however, were markedly altered after long-term treatment with endothelin receptor antagonists in a blood pressure\u2013independent manner. These 2 effects are mediated by different subtypes of endothelin receptors. ETA receptor blockade completely normalized the hypertrophy of intracardiac arteries (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01 compared with 2K1C without treatment) in renovascular hypertension, whereas the ETB antagonist reduced cardiac fibrosis of the left ventricle (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001 compared with 2K1C without treatment) to baseline values. This study demonstrates that the cardiac endothelin system plays an important role in the development of cardiac fibrosis as well as in hypertrophy of intracardiac arteries in 2K1C renovascular hypertensive rats.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.33.3.816","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"816-822","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":81,"title":["Endothelin System\u2013Dependent Cardiac Remodeling in Renovascular Hypertension"],"prefix":"10.1161","volume":"33","author":[{"given":"Berthold","family":"Hocher","sequence":"first","affiliation":[{"name":"From the Department of Nephrology, Universita\u0308tsklinikum Charite\u0301 der Humboldt Universita\u0308t zu Berlin (B.H., J.R., A.S., H.-H.N.), and the Institute of Molecular Biology and Biochemistry, Free University of Berlin (B.H., I.G., J.R., A.B., A.S., C.B.), Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"George","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, Universita\u0308tsklinikum Charite\u0301 der Humboldt Universita\u0308t zu Berlin (B.H., J.R., A.S., H.-H.N.), and the Institute of Molecular Biology and Biochemistry, Free University of Berlin (B.H., I.G., J.R., A.B., A.S., C.B.), Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Rebstock","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, Universita\u0308tsklinikum Charite\u0301 der Humboldt Universita\u0308t zu Berlin (B.H., J.R., A.S., H.-H.N.), and the Institute of Molecular Biology and Biochemistry, Free University of Berlin (B.H., I.G., J.R., A.B., A.S., C.B.), Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Bauch","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, Universita\u0308tsklinikum Charite\u0301 der Humboldt Universita\u0308t zu Berlin (B.H., J.R., A.S., H.-H.N.), and the Institute of Molecular Biology and Biochemistry, Free University of Berlin (B.H., I.G., J.R., A.B., A.S., C.B.), Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Schwarz","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, Universita\u0308tsklinikum Charite\u0301 der Humboldt Universita\u0308t zu Berlin (B.H., J.R., A.S., H.-H.N.), and the Institute of Molecular Biology and Biochemistry, Free University of Berlin (B.H., I.G., J.R., A.B., A.S., C.B.), Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-H.","family":"Neumayer","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, Universita\u0308tsklinikum Charite\u0301 der Humboldt Universita\u0308t zu Berlin (B.H., J.R., A.S., H.-H.N.), and the Institute of Molecular Biology and Biochemistry, Free University of Berlin (B.H., I.G., J.R., A.B., A.S., C.B.), Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Bauer","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, Universita\u0308tsklinikum Charite\u0301 der Humboldt Universita\u0308t zu Berlin (B.H., J.R., A.S., H.-H.N.), and the Institute of Molecular Biology and Biochemistry, Free University of Berlin (B.H., I.G., J.R., A.B., A.S., C.B.), Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"crossref","unstructured":"Brilla CG. The cardiac structure-function relationship and the renin-angiotensin-aldosterone system in hypertension and heart failure. Curr Opin Cardiol. 1994;9(suppl 1):S2\u2013S10.","DOI":"10.1097\/00001573-199407000-00002"},{"key":"e_1_3_2_2_2","first-page":"1G","volume":"65","year":"1990","unstructured":"Weber KT, Janicki JS, Pick R, Capasso J, Anversa P. Myocardial fibrosis and pathologic hypertrophy in the rat with renovascular hypertension. Am J Cardiol. 1990;65:1G\u20137G.","journal-title":"Am J Cardiol"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.29.1.435"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.5.1593"},{"key":"e_1_3_2_5_2","first-page":"175","volume":"35","year":"1997","unstructured":"Hocher B, Th\u00f6ne-Reineke C, Bauer C, Raschack M, Neumayer HH. The paracrine endothelin system; pathophysiology and implications in clinical medicine. Eur J Clin Chem Clin Biochem. 1997;35:175\u2013189.","journal-title":"Eur J Clin Chem Clin Biochem"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.6.3221"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116579"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199309000-00006"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.6.1976"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/27.12.2130"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150191124"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15390.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.28.2.196"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V971169"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119297"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/22.10.686"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"12A","DOI":"10.1016\/0002-9149(93)90239-9","volume":"71","year":"1993","unstructured":"Brilla C, Matsubara L, Weber KT. Antihypertensive effects of spironolactone in myocardial fibrosis in systemic arterial hypertension. Am J Cardiol. 1993;71:12A\u201316A.","journal-title":"Am J Cardiol"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116579"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199800001-00108"},{"key":"e_1_3_2_21_2","first-page":"H88","volume":"271","year":"1996","unstructured":"Li JS, Knafo L, Turgeon A, Garcia R, Schiffrin E. Effect of endothelin antagonism on blood pressure and vascular structure in renovascular hypertensive rats. Am J Physiol. 1996;271:H88\u2013H93.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(76)92165-6"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.25.2.288"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00167-J"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(95)91911-2"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.89.5.8181145"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb13273.x"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb14780.x"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/27.12.2125"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/27.12.2130"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1997.273.5.E922"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118092"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.6.1976"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(95)00201-4"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001573-199707000-00003"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.15.10050"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.272.6.C1810"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199601000-00022"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-199711000-00010"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","unstructured":"Sihm I Schroeder AP Aalkjaer C Holm M Morn B Mulvany M. Thygesen K Lederballe O. Regression of media-to-lumen ratio of human subcutaneous arteries and left ventricular hypertrophy during treatment with an angiotensin-converting enzyme inhibitor-based regimen in hypertensive patients. Am J Cardiol. 1995 24;76:38E\u201340E.","DOI":"10.1016\/S0002-9149(99)80502-5"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.33.3.816","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T17:27:51Z","timestamp":1715534871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.33.3.816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,3]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1999,3]]}},"alternative-id":["10.1161\/01.HYP.33.3.816"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.33.3.816","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,3]]},"assertion":[{"value":"1998-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-11-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}