Epidemiological evidence suggests that populations consuming large amounts of soy have a reduced incidence of coronary heart disease (Lissin & Cooke, 2000). Standard rat chow contains soy and is therefore rich in phytoestrogens. We have investigated the effects of soy-free vs. soy containing diets on oxidative stress and endothelial function ex vivo and arterial blood pressure in vivo in male Wistar rats reared on a soy containing or a soy-free diet for 12-16 months (Atanassova et al. 2000). Aortic rings and isolated mesenteric and main pulmonary arteries were preconstricted with phenylephrine and exposed to increasing concentrations of either acetylcholine or carbachol. Blood pressure was monitored using telemetric devices in contious and freely moving animals. Acetylcholine induced relaxation was significantly reduced in endothelium intact aortic rings from rats fed a soy-free diet for 12 or 16 months compared to those maintained on a soy containing diet (38±2% vs 60±2%, n=6-7, P≤0.001). Similar findings were observed in the isolated perfused mesentery and main pulmonary artery rings (300-400 nm). Relaxation to the nitric oxide donor sodium nitroprusside was unaffected by dietary manipulations. Impaired vascular reactivity in soy-deficient animals was paralleled by significantly decreased mitochondrial glutathione and 3-fold lower mRNA levels for eNOS and the antioxidant enzymes Mn-SOD and cytochrome c oxidase (n=4-5). Moreover, rats fed the soy free diet for 16 months had significantly increased systolic (150±2 vs 142±1 mmHg, n=4-5, P≤0.05) and diastolic (108±1 vs 101±1, n=4-5, P≤0.05) blood pressures compared to animals on the soy diet. When soy-free rats were switched to a soy diet for 6 months, impaired eNOS and antioxidant gene expression, as well as endothelial dysfunction in vitro and arterial blood pressure in vivo were restored to values in age-matched animals fed the soy diet. These results suggest that a soy rich diet increases eNOS and antioxidant gene expression in the vasculature, resulting in enhanced NO bioavailability and protection against oxidative stress. The reversal of endothelial dysfunction, impaired gene expression and hypertension by dietary soy isoflavones may be of relevance to patients at risk of coronary heart disease.