Aortic smooth muscle cell proliferation and endothelial nitric oxide synthase activity in fructose-fed rats

Am J Hypertens. 2001 Nov;14(11 Pt 1):1135-41. doi: 10.1016/s0895-7061(01)02206-3.


The aim of this study was to evaluate the proliferative behavior of vascular smooth muscle cells in primary culture (pC-SMC) and the endothelial nitric oxide synthase (eNOS) activity in the endothelial lining of the aorta of fructose-fed rats (FFR). This is an experimental model of syndrome X, a cluster of cardiovascular risk factors including hyperinsulinemia, insulin resistance, and hypertension that has been suggested to be of pathophysiologic importance for the development of atherosclerosis. Male Wistar rats were used: Control (n = 12) and FFR (n = 12). After receiving fructose in drinking water (10% w/v) during 8 weeks, biochemical parameters, systolic blood pressure (SBP) and relative heart weight (RHW) were determined. The proliferative effect of 10% fetal calf serum (FCS) was examined in aortic pC-SMC by [3H]thymidine incorporation and by cell counting. Ca2+/calmodulin-dependent NOS activity was estimated in aortic endothelial lining and in heart tissue homogenates by conversion of [3H]arginine into [3H]citrulline. Fructose-fed rats showed hyperinsulinemia (P = .0263), altered glucose tolerance test (P < .001), higher SBP (P < .0001), and RHW (P = .0145), compared to control rats. These animals also showed an increase of 10% FCS-induced [3H]thymidine incorporation (P < .0001) and cell number of aortic pC-SMC (P = .0049) and decreased eNOS activity in both aortic endothelium (P = .0147) and cardiac tissue (P < .0001). These data support the hypothesis that syndrome X is associated to changes in SMC proliferation and endothelial dysfunction, which could be involved in the onset or progression of the atherogenic process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta* / cytology
  • Aorta* / enzymology
  • Arteriosclerosis / etiology
  • Cell Division
  • Dietary Carbohydrates / adverse effects
  • Dietary Carbohydrates / metabolism
  • Fructose / adverse effects
  • Fructose / metabolism*
  • Male
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / enzymology*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type III
  • Rats
  • Rats, Wistar
  • Risk Factors


  • Dietary Carbohydrates
  • Fructose
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat