(Circulation. 2001;103:3136.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Long-Term Effect of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline on Left Ventricular Collagen Deposition in Rats With 2-Kidney, 1-Clip Hypertension
From the Hypertension and Vascular Research Division (N.-E.R., H.P., X.-P.Y., Y.-H.L., D.M., O.A.C.), Henry Ford Hospital, Detroit, Mich, and CEA (E.E.), Service de Pharmacologie et d’Immunologie, Saclay, Gif-sur-Yvette, France.
Correspondence to Nour-Eddine Rhaleb, PhD, Education and Research Suite 7015, Henry Ford Hospital, Hypertension and Vascular Research Division, 2799 W Grand Blvd, Detroit, MI 48202-2689. E-mail nrhaleb1{at}hfhs.org
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 µg · 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.
Key Words: angiotensin • hypertension, renal • blood pressure • inhibitors • collagen • myocardium
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