It became evident in the present study that carbon tetrachloride (CCl4), in addition to its known liver and renal toxicity, causes serious damage to endothelial cells. The preventive effect of red wine on cardiovascular diseases has been documented in a number of human population studies as well as in animal experimental models. In this study, the endothelium protective effect of polyphenolic compounds isolated from red wine was studied in rats administered 0.5 ml of CCl4/kg body weight intraperitoneally twice a week for 8 weeks. Endothelemia (endothelial cells/10 μl of plasma) was used as the marker of endothelial cell injury in vivo. Chronic CCl4 treatment for 8 weeks lead to a 3-fold increase of free endothelial cells circulating in the blood when compared to the baseline values (2.5±0.3). Parallel oral administration of polyphenols 40 mg/kg/day significantly decreased the endothelemia. Polyphenolic compounds alone did not produce significant changes. Three weeks of spontaneous recovery after the 8-week treatment with CCl4 did not lead to a marked decrease of endothelemia, but the administration of red wine polyphenols during the 3-week period significantly decreased free endothelial cells in the blood. It can be concluded that long-term administration of CCl4 may serve as a useful experimental model of endothelial damage. The red wine polyphenolic compounds exert a powerful protective effect on endothelial cells from the injury caused by CCl4. This effect was documented by decreased endothelemia that corresponded to diminished endothelial cell swelling and detachment evaluated by histology of the vascular intima. The endothelium protective effect may be one of the key factors that contribute to the preventive action of red wine on cardiovascular diseases.
The imbalance between nitric oxide (NO) and reactive oxygen species (ROS) production appears to be a common feature of experimental and human hypertension. Previously, different antioxidants and/or scavengers of oxygen free radicals were shown to activate nitric oxide synthase (NO synthase, NOS) and to increase the expression of both endothelial and neuronal NO synthase isoforms leading to blood pressure reduction. On the other hand, various antihypertensive drugs have been documented to possess antioxidant properties, which may contribute to their beneficial effect on blood pressure. This review is focused on the effects of antioxidant treatment in different models of
experimental hypertension with a special attention to the prevention of oxidative damage and the augmentation of NO synthase activity and expression of NOS isoforms.