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Chronic administration of losartan reverses cardiovascular changes in hypertensive fructose-fed rats.

Authors
  • Miatello, R
  • Risler, N
  • Castro, C
  • Cruzado, M
  • González, S
  • Zumino, A Ponce
Type
Published Article
Journal
Cellular and molecular biology (Noisy-le-Grand, France)
Publication Date
Sep 01, 2003
Volume
49
Issue
6
Pages
945–952
Identifiers
PMID: 14656052
Source
Medline
License
Unknown

Abstract

The cluster of risk factors including hyperinsulinemia, insulin resistance, hypertriglyceridemia and hypertension has been called syndrome X. Several evidences link the insulin resistance syndrome with endothelial dysfunction. Since the participation of the renin-angiotensin system (RAS) in this pathology is still unclear, the present study examined the effect of chronic administration of an angiotensin AT1 receptor antagonist, losartan (L), on endothelial nitric oxide synthase (eNOS) activity in aortic endothelium and cardiac tissue, and on the proliferation of primary cultured aortic smooth muscle cells (SMC), obtained from fructose-fed rats (FFR), an experimental model of syndrome X Male Wistar rats were used: Control, FFR and FFR+L (n = 8 in each group). After 8 weeks, tissue samples were obtained and 10% fetal calf serum (FCS) proliferative effect was examined in SMC by 3H-thymidine incorporation and cell counting. The eNOS activity was estimated in aortic endothelial lining and cardiac homogenates by conversion of 3H-arginine into 3H-citrulline. FFR aortic SMC showed a significantly increased 10% FCS-induced 3H-thymidine incorporation and cell number compared to controls. FFR aortic and cardiac eNOS activities were significantly decreased. Chronic treatment with L decreased systolic blood pressure,reverted cardiac hypertrophy, abolished the increased SMC proliferation and restoredeNOS activity. These data confirm that changes in SMC proliferation and endothelial dysfunction at different levels of the cardiovascular system are involved in syndrome "X", and that AT1 receptor blocking can revert those changes, suggesting an important role of the RAS, possibly mediated by AT2 receptors and kinins, in the physiopathological mechanisms of this model.

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