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

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 [H-3]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 [H-3]arginine into [H-3]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 [H-3]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. Am J Hypertens 2001;14:1135-1141 (C) 2001 American Journal of Hypertension, Ltd.