{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:45:42Z","timestamp":1791323142606,"version":"4.3.1"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2001,1,16]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014To test the hypothesis that endothelin-1 contributes to cardiac fibrosis, cardiac collagen deposition was studied in deoxycorticosterone acetate\u2013salt (DOCA-salt) hypertensive rats, in which the endothelin system is activated. The effects of the ET\n            <jats:sub>A<\/jats:sub>\n            -selective endothelin receptor antagonist A-127722 were evaluated.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014A-127722 (30 mg\/kg per day) was administered for 4 weeks. Myocardial fibrosis was evaluated after Sirius red F3BA staining. Systolic blood pressure was 103\u00b11.6 mm Hg in unilaterally nephrectomized rats (Uni-Nx), 202\u00b13.2 mm Hg in DOCA-salt rats (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01 versus Uni-Nx), and 182\u00b13.1 mm Hg in ET\n            <jats:sub>A<\/jats:sub>\n            antagonist\u2013treated DOCA-salt rats (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01 versus DOCA-salt or Uni-Nx). In DOCA-salt rats, interstitial and perivascular collagen density was increased in the subendocardial and midmyocardial regions of the left ventricle (3- to 4-fold,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05), whereas in subepicardial myocardium, the increase was predominantly perivascular. The ET\n            <jats:sub>A<\/jats:sub>\n            antagonist prevented cardiac fibrosis in DOCA-salt rats. Procollagen I and III mRNA, which were increased in hearts of DOCA-salt rats, were normalized by ET\n            <jats:sub>A<\/jats:sub>\n            antagonist treatment. TGF-\u03b2\n            <jats:sub>1<\/jats:sub>\n            mRNA and TGF-\u03b2\n            <jats:sub>1<\/jats:sub>\n            protein increased at 1 week in DOCA-salt rats and were lowered in ET\n            <jats:sub>A<\/jats:sub>\n            antagonist\u2013treated rats.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014ET\n            <jats:sub>A<\/jats:sub>\n            receptor\u2013mediated collagen deposition in hearts of DOCA-salt rats results from increased procollagen synthesis associated with an initial increment in expression of TGF-\u03b2\n            <jats:sub>1<\/jats:sub>\n            . These results support the hypothesis of a role for endothelin-1 in cardiac collagen deposition in mineralocorticoid hypertension, which may have pathophysiological and pharmacological implications in hypertensive heart disease.\n          <\/jats:p>","DOI":"10.1161\/01.cir.103.2.319","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:09:32Z","timestamp":1339459772000},"page":"319-324","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":119,"title":["Myocardial Fibrosis in DOCA-Salt Hypertensive Rats"],"prefix":"10.1161","volume":"103","author":[{"given":"Fatima","family":"Ammarguellat","sequence":"first","affiliation":[{"name":"From the Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Larouche","sequence":"additional","affiliation":[{"name":"From the Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto L.","family":"Schiffrin","sequence":"additional","affiliation":[{"name":"From the Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.4.C873"},{"key":"e_1_3_2_2_2","first-page":"1G","volume":"65","year":"1990","unstructured":"Weber KT, Janicki JS, Pick R, et al. 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