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This Article Full Text Full Text (PDF) All Versions of this Article: 292/4/H1931    most recent 00755.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Rietjens, S. J. Articles by Haenen, G. R. M. M. Search for Related Content PubMed PubMed Citation Articles by Rietjens, S. J. Articles by Haenen, G. R. M. M.

The olive oil antioxidant hydroxytyrosol efficiently protects against the oxidative stress-induced impairment of the NO response of isolated rat aorta

Departments of ¹Pharmacology and Toxicology and ²Psychiatry and Neuropsychology, Faculty of Medicine, Maastricht University, Maastricht, The Netherlands

Submitted 13 July 2006 ; accepted in final form 8 December 2006

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 (NO)-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 (OH). CHP (300 µM) impaired the NO-mediated relaxation of rat aorta by the acetylcholine receptor agonist carbachol (P < 0.05). This was due to a reduction in NO production. A diminished NO-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 µM) efficiently protected the aorta against the CHP-induced impairment of the NO-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 OH scavenger, which can be attributed to its catechol moiety. Because of its amphiphilic characteristics (octanol-water 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