Isoflavones, which are found in high concentrations in soy protein, are proposed to be cardioprotective. It has been demonstrated in female spontaneously hypertensive rats, that soy extracts lowered blood pressure, and ovariectomized rats fed a diet rich in isoflavones have improved endothelial function. The aim of this study was to investigate the cardiovascular effects of soy-derived isoflavones in male and female rats, using diets identical in nutrient composition except with regard to the isoflavone content. Male and female Wistar rats were fed either a low (LI) (0.04 mg/g) or high (HI) (0.2 mg/g) isoflavone-containing diet and mated. Offspring were weaned onto and maintained on the same diet as their dam and sire. At 6 months of age, animals were implanted (under 4% isofluorane in oxygen anaesthesia) with a radio-telemetric cardiovascular monitoring device (DSI, USA). Data were collected every 5 min over a 1 week period and 12h day and night averages calculated. Animals were then humanely killed. Third order mesenteric arteries were dissected and mounted on a small vessel myograph (DMT, Denmark). Dose-response curves to noradrenaline (1×10^-7-1×10^-5), endothelin-1 (1×10^-10-3×10^-8), acetylcholine (1×10^-9-1×10^-5) and nitric oxide (1×10^-7-1×10^-4) were obtained (noradrenaline was used as the pre-constrictor). Vascular function data were assessed using repeated measure ANOVA and one-way ANOVA; radio-telemetric data were assessed using multiple regression with robust standard errors. P<0.05 was considered significant. When results for males and females did not differ, data were combined. Data are presented as the mean ± SEM. A significant effect of diet on the response to acetylcholine-induced relaxation was observed. Male and female animals fed the LI diet demonstrated decreased sensitivity to acetylcholine compared with animals fed the HI diet (pEC50 LI 6.77 ± 0.1, n=16 versus HI, 7.31 ± 0.1, n=20, P<0.05). There was no difference in systolic (LI 121 ± 1 mmHg n=16, HI 118 ± 1, n=20) or diastolic blood pressure (LI 92 ± 0.7 mmHg n=16, HI 90 ± 1, n=20), heart rate (LI 383 ± 4 beats/min n=16, HI 383 ± 4, n=20) or activity (LI 3.68 ± 0.12 arbitrary units n=16, HI 3.67 ± 0.198, n=20) between the two dietary groups. Feeding a HI diet compared with a LI diet did not alter responses in mesenteric arteries to noradrenaline, endothelin-1 or nitric oxide. In conclusion, life long consumption of a diet high in isoflavones appears to increase endothelial-dependent dilatation but has no effect on blood pressure or heart rate in 6 month old rats