Document Detail

Long-term effect of N-acetyl-seryl-aspartyl-lysyl-proline on left ventricular collagen deposition in rats with 2-kidney, 1-clip hypertension.
MedLine Citation:
PMID:  11425781     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural inhibitor of pluripotent hematopoietic stem cell proliferation. Ac-SDKP plasma concentration is increased 5-fold after angiotensin-converting enzyme inhibition. Here we studied the effect of Ac-SDKP on monocyte/macrophage infiltration, fibroblast proliferation, and collagen deposition in the rat heart in renovascular hypertension.
METHODS AND RESULTS: We investigated whether long-term Ac-SDKP administration would prevent left ventricular (LV) hypertrophy and interstitial collagen deposition in rats with 2-kidney, 1-clip (2K-1C) hypertension. Ac-SDKP (400 microgram. kg(-1). d(-1)) did not affect development of hypertension. Mean blood pressure was similar in rats with 2K-1C hypertension whether they were given vehicle or Ac-SDKP and was higher than in controls. Both LV weight and cardiomyocyte size were significantly increased in rats with 2K-1C hypertension compared with controls and were unaffected by Ac-SDKP. Proliferating cell nuclear antigen- and monocyte/macrophage-positive cells were increased in the LV of 2K-1C hypertensive rats; this increase was significantly blunted by Ac-SDKP (P<0.001). LV interstitial collagen fraction was also increased in 2K-1C hypertensive rats given vehicle (10.1+/-0.8%) compared with sham (5.3+/-0.1%, P<0.0001), and this increase was prevented by Ac-SDKP (5.4+/-0.4%, P<0.001).
CONCLUSIONS: Ac-SDKP inhibited monocyte/macrophage infiltration, cell proliferation, and collagen deposition in the LV of hypertensive rats without affecting blood pressure or cardiac hypertrophy, suggesting that it may be partly responsible for the cardioprotective effect of angiotensin-converting enzyme inhibitors.
N E Rhaleb; H Peng; X P Yang; Y H Liu; D Mehta; E Ezan; O A Carretero
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  103     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-06-26     Completed Date:  2001-08-09     Revised Date:  2012-10-09    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3136-41     Citation Subset:  AIM; IM    
Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan, USA.
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MeSH Terms
Blood Pressure / drug effects
Cell Division / drug effects
Collagen / drug effects*,  metabolism
Dose-Response Relationship, Drug
Heart / drug effects
Heart Rate / drug effects
Heart Ventricles / drug effects*,  metabolism
Hypertension, Renovascular / metabolism*,  physiopathology
Hypertrophy, Left Ventricular / pathology
Macrophages / drug effects,  pathology
Monocytes / drug effects,  pathology
Myocardium / pathology
Oligopeptides / blood,  pharmacology*
Rats, Sprague-Dawley
Time Factors
Grant Support
Reg. No./Substance:
0/Oligopeptides; 120081-14-3/goralatide; 9007-34-5/Collagen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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