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(Hypertension. 2001;37:794.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Antifibrotic Effects of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline on the Heart and Kidney in Aldosterone-Salt Hypertensive Rats

Hongmei Peng; Oscar A. Carretero; Leopoldo Raij; Fang Yang; Alissa Kapke; Nour-Eddine Rhaleb

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).

Correspondence to Nour-Eddine Rhaleb, PhD, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202-2689. E-mail nrhaleb1{at}hfhs.org

N-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 µg/h SC) and 1% NaCl/0.2% KCl in drinking water (ALDO-salt), (3) rats that received ALDO-salt plus Ac-SDKP 400 µg · kg^-1 · day^-1 SC, and (4) rats that received ALDO-salt plus Ac-SDKP 800 µg · kg^-1 · d^-1 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 (P<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 (P<0.0001), and significantly increased interstitial and perivascular PCNA-positive cells in the LV and kidney (P<0.0001). Ac-SDKP at 800 µg · kg^-1 · d^-1 markedly prevented cardiac and renal fibrosis (P<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.

Key Words: aldosterone • hypertension, mineralocorticoid • collagen • heart • kidney

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