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

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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 800μg · 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.

Original languageEnglish
Pages (from-to)794-800
Number of pages7
JournalHypertension
Volume37
Issue number2 II
StatePublished - Mar 19 2001
Externally publishedYes

Fingerprint

Aldosterone
Salts
Kidney
Heart Ventricles
Collagen
Proliferating Cell Nuclear Antigen
Fibrosis
Renin
Hypertrophy
Cell Proliferation
Blood Pressure
Angiotensin-Converting Enzyme Inhibitors
goralatide
Renovascular Hypertension
Drinking Water
Fibroblasts
Body Weight
Hypertension
Control Groups
Water

Keywords

  • Aldosterone
  • Collagen
  • Heart
  • Hypertension
  • Kidney
  • Mineralocorticoid

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Peng, H., Carretero, O. A., Raij, L., Yang, F., Kapke, A., & Rhaleb, N. E. (2001). Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats. Hypertension, 37(2 II), 794-800.

Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats. / Peng, Hongmei; Carretero, Oscar A.; Raij, Leopoldo; Yang, Fang; Kapke, Alissa; Rhaleb, Nour Eddine.

In: Hypertension, Vol. 37, No. 2 II, 19.03.2001, p. 794-800.

Research output: Contribution to journalArticle

Peng, H, Carretero, OA, Raij, L, Yang, F, Kapke, A & Rhaleb, NE 2001, 'Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats', Hypertension, vol. 37, no. 2 II, pp. 794-800.
Peng H, Carretero OA, Raij L, Yang F, Kapke A, Rhaleb NE. Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats. Hypertension. 2001 Mar 19;37(2 II):794-800.
Peng, Hongmei ; Carretero, Oscar A. ; Raij, Leopoldo ; Yang, Fang ; Kapke, Alissa ; Rhaleb, Nour Eddine. / Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats. In: Hypertension. 2001 ; Vol. 37, No. 2 II. pp. 794-800.
@article{e992299fba274182990063d6850d8ba7,
title = "Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats",
abstract = "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 800μg · 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.",
keywords = "Aldosterone, Collagen, Heart, Hypertension, Kidney, Mineralocorticoid",
author = "Hongmei Peng and Carretero, {Oscar A.} and Leopoldo Raij and Fang Yang and Alissa Kapke and Rhaleb, {Nour Eddine}",
year = "2001",
month = "3",
day = "19",
language = "English",
volume = "37",
pages = "794--800",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "2 II",

}

TY - JOUR

T1 - Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats

AU - Peng, Hongmei

AU - Carretero, Oscar A.

AU - Raij, Leopoldo

AU - Yang, Fang

AU - Kapke, Alissa

AU - Rhaleb, Nour Eddine

PY - 2001/3/19

Y1 - 2001/3/19

N2 - 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 800μg · 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.

AB - 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 800μg · 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.

KW - Aldosterone

KW - Collagen

KW - Heart

KW - Hypertension

KW - Kidney

KW - Mineralocorticoid

UR - http://www.scopus.com/inward/record.url?scp=0035095260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035095260&partnerID=8YFLogxK

M3 - Article

C2 - 11230375

AN - SCOPUS:0035095260

VL - 37

SP - 794

EP - 800

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 2 II

ER -