- Aim of the study: Hypercholesterolemia increases oxidative stress and impairs endothelium-dependent relaxation. In this study the effect of the short term (30 days) administration with the pummelo juice extract on the release of superoxide and vascular function in aortae frome hypercholesterolemic rats was investigated. Materials and Methods: Hypercholesterolemia induced by a high-cholesterol diet in rats. Vascular reactivity and superoxide generation were assessed in aortic rings using organ bath techniques and lucigenin-enhanced chemiluminescence, respectively. Results: Aortic rings from normal rats were acutely exposed to pummelo juice extract there was significant reduction in the detection of superoxide anion. Eight weeks after the cholesterol diet-induced hypercholesterolemic rats the levels of total cholesterol (TC) and LDL were elevated compared to control rats and there was an increased aortic generation of superoxide anion. In aortic rings from hypercholesterolemic rats acetylcholine (ACh)-induced relaxation was impaired whereas endothelium-independent releaxation to sodium nitroprusside (SNP) was unaffected. The cholesterol diet-induced hypercholesterolemic rats were orally administered daily with pummelo juice extract (1 and 10 mg/kg/day) for 4 weeks. Chronic pummelo juice extract treatment decreased the levels of TC and LDL and reduced aortic superoxide generation in hypercholesterolemic rats. In addition the relaxation to ACh and aortic nitrite/nitrate were increased in pummelo extract treated-hypercholesterolemic rats. Conclusion: These results suggest that chronic administration of pummelo juice extract reduces oxidative stress and preserves endothelium-dependent relaxation in aortae from hypercholesterolemic rats.