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 language | English |
|---|---|
| Pages (from-to) | 794-800 |
| Number of pages | 7 |
| Journal | Hypertension |
| Volume | 37 |
| Issue number | 2 II |
| State | Published - Mar 19 2001 |
| Externally published | Yes |
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Keywords
- Aldosterone
- Collagen
- Heart
- Hypertension
- Kidney
- Mineralocorticoid
ASJC Scopus subject areas
- Internal Medicine
Cite this
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 journal › Article
}
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 -