{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:27:12Z","timestamp":1790918832912,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2001,2]]},"abstract":"<jats:p><jats:italic>N<\/jats:italic>-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibits not only hematopoietic cell proliferation but also fibroblast proliferation and collagen synthesis in vitro. Ac-SDKP also prevents collagen deposition and cell proliferation in the left ventricle (LV) in rats with renovascular hypertension (renin dependent). However, it is not clear whether Ac-SDKP has similar effects in a model of renin-independent hypertension (aldosterone-salt). Using a hypertensive rat model of cardiac and renal fibrosis created by chronic elevation of circulating aldosterone (ALDO) levels, we examined the effect of Ac-SDKP on blood pressure, cardiac and renal fibrosis and hypertrophy, and proliferating cell nuclear antigen (PCNA) expression in the LV and left kidney. Uninephrectomized rats were divided into 4 groups: (1) controls that received tap water, (2) rats that received ALDO (0.75 \u03bcg\/h SC) and 1% NaCl\/0.2% KCl in drinking water (ALDO-salt), (3) rats that received ALDO-salt plus Ac-SDKP 400 \u03bcg \u00b7 kg<jats:sup>\u22121<\/jats:sup>\u00b7 day<jats:sup>\u22121<\/jats:sup>SC, and (4) rats that received ALDO-salt plus Ac-SDKP 800 \u03bcg \u00b7 kg<jats:sup>\u22121<\/jats:sup>\u00b7 d<jats:sup>\u22121<\/jats:sup>SC. After 6 weeks of treatment, the ALDO-salt group was found to have significantly increased blood pressure with decreased body weight and plasma renin concentration (<jats:italic>P<\/jats:italic>&lt;0.05), LV and renal hypertrophy as well as renal injury, significantly increased collagen content in both ventricles and kidney as well as increased collagen volume fraction in the LV (<jats:italic>P<\/jats:italic>&lt;0.0001), and significantly increased interstitial and perivascular PCNA-positive cells in the LV and kidney (<jats:italic>P<\/jats:italic>&lt;0.0001). Ac-SDKP at 800 \u03bcg \u00b7 kg<jats:sup>\u22121<\/jats:sup>\u00b7 d<jats:sup>\u22121<\/jats:sup>markedly prevented cardiac and renal fibrosis (<jats:italic>P<\/jats:italic>&lt;0.005) without affecting blood pressure or organ hypertrophy. It also suppressed PCNA expression in the LV and kidney in a dose-dependent manner. We concluded that Ac-SDKP prevents increased collagen deposition and cell proliferation in the heart and kidney in ALDO-salt hypertensive rats. Because ACE inhibitors increase plasma and tissue Ac-SDKP and decrease cardiac and renal fibrosis, we speculate that Ac-SDKP may participate in the antifibrotic effect of ACE inhibitors.<\/jats:p>","DOI":"10.1161\/01.hyp.37.2.794","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"794-800","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":76,"title":["Antifibrotic Effects of<i>N<\/i>-Acetyl-Seryl-Aspartyl-Lysyl-Proline on the Heart and Kidney in Aldosterone-Salt Hypertensive Rats"],"prefix":"10.1161","volume":"37","author":[{"given":"Hongmei","family":"Peng","sequence":"first","affiliation":[{"name":"From the Hypertension and Vascular Research Division (H.P., O.A.C., F.Y., N.-E.R.), Department of Biostatistics and Research Epidemiology (A.K.), Henry Ford Hospital, Detroit, Mich; and Veterans Affairs Medical Center (L.R.), University of Minnesota Medical School (Minneapolis)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar A.","family":"Carretero","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division (H.P., O.A.C., F.Y., N.-E.R.), Department of Biostatistics and Research Epidemiology (A.K.), Henry Ford Hospital, Detroit, Mich; and Veterans Affairs Medical Center (L.R.), University of Minnesota Medical School (Minneapolis)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leopoldo","family":"Raij","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division (H.P., O.A.C., F.Y., N.-E.R.), Department of Biostatistics and Research Epidemiology (A.K.), Henry Ford Hospital, Detroit, Mich; and Veterans Affairs Medical Center (L.R.), University of Minnesota Medical School (Minneapolis)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yang","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division (H.P., O.A.C., F.Y., N.-E.R.), Department of Biostatistics and Research Epidemiology (A.K.), Henry Ford Hospital, Detroit, Mich; and Veterans Affairs Medical Center (L.R.), University of Minnesota Medical School (Minneapolis)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alissa","family":"Kapke","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division (H.P., O.A.C., F.Y., N.-E.R.), Department of Biostatistics and Research Epidemiology (A.K.), Henry Ford Hospital, Detroit, Mich; and Veterans Affairs Medical Center (L.R.), University of Minnesota Medical School (Minneapolis)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour-Eddine","family":"Rhaleb","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division (H.P., O.A.C., F.Y., N.-E.R.), Department of Biostatistics and Research Epidemiology (A.K.), Henry Ford Hospital, Detroit, Mich; and Veterans Affairs Medical Center (L.R.), University of Minnesota Medical School (Minneapolis)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.3.779"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.11.3307.3307"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(90)90489-A"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118484"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.30.5.1015"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/S0022-3565(24)38267-9","volume":"289","year":"1999","unstructured":"Junot C, Menard J, Gonzales M-F, Michaud A, Corvol P, Ezan E. 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