The olive oil antioxidant hydroxytyrosol efficiently protects against the oxidative stress-induced impairment of the N[O.sup.*] response of isolated rat aorta

The Mediterranean diet, which is abundant in antioxidants, is associated with a relatively low incidence of coronary heart disease. Olive oil and olives, which contain the antioxidants hydroxytyrosol, oleuropein, and tyrosol, are important components of this diet. In this study, the effects of oxidative stress on the nitric oxide radical (N[O.sup.*])-mediated relaxation of rat aorta and the protection by these antioxidants were determined. Cumene hydroperoxide (CHP) was used to mimic oxidative stress induced by lipid hydroperoxides, which is mediated by the formation of hydroxyl radicals (O[H.sup.*]). CHP (300 [micro]M) impaired the N[O.sup.*]-mediated relaxation of rat aorta by the acetylcholine receptor agonist carbachol (P < 0.05). This was due to a reduction in N[O.sup.*] production. A diminished N[O.sup.*]- mediated relaxation disturbs the vascular tone and leads to a rise in blood pressure, which is a well-established risk factor for coronary heart disease. Hydroxytyrosol (10 [micro]M) efficiently protected the aorta against the CHP-induced impairment of the N[O.sup.*]-mediated relaxation (P < 0.05). Oleuropein, tyrosol, and homovanillic alcohol, a major metabolite of hydroxytyrosol, did not show protection. Moreover, hydroxytyrosol was found to be a potent O[H.sup.*] scavenger, which can be attributed to its catechol moiety. Because of its amphiphilic characteristics (octanolwater partitioning coefficient = 1.1), hydroxytyrosol will readily cross membranes and provide protection in the cytosol and membranes, including the water-lipid interface. The present study provides a molecular basis for the contribution of hydroxytyrosol to the benefits of the Mediterranean diet. nitric oxide; lipophilicity; hydroxyl radical; cumene hydroperoxide; Mediterranean diet