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Anti-Atherogenic Effect of Oleanolic Acid Appears Unrelated to Endothelial Release of Nitric Oxide
Simonsen, Ulf | Department of Pharmacology, University of Aarhus, Aarhus, Denmark |
Hansson, Nicolaj | Department of Pharmacology, University of Aarhus, Aarhus, Denmark |
Rodriguez-Rodriguez, Rosalía | Department of Pharmacology, University of Aarhus, Aarhus, Denmark |
Andersen, Malene R | Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark |
Department of Pharmacology, University of Aarhus, Aarhus, Denmark | |
Buus, Niels Henrik | Department of Pharmacology, University of Aarhus, Aarhus, Denmark |
Eskildsen-Helmond, Yvonne | Department of Pharmacology, University of Aarhus, Aarhus, Denmark |
| Date Issued |
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2009-06-01 |
The present study investigated the mechanisms by which oleanolic acid, a component of olive oil, increases release of nitric oxide (NO), and investigated the effect of oleanolic acid in an atherosclerotic animal model. Measurements of isometric tension, NO concentration, and endothelial cell calcium were performed in isolated rat mesenteric arteries. 8 weels ApoE-/- miee were feed a Western-type diet in combination with oleanolic acid (ApoE-/- -OA; 100 mg/kg/day), fluvastatin (ApoE-/--fluvastatin; 5 mg/kg/day), or vehicle (ApoE-/-- Vehicle). Wild type mice were used as negative controls. Oleanolic acicd, caused endothelium-dependent relaxation in large and small mesenteric arteries from rats. The release of NO was calcium-independent and due to phosphorylation of Akt and endothelial NO synthase at serine 1177. ln the animal study total plasma cholesterol levels were similar among all groups of ApoE-/-mice, while atherosclerotic plaque area was reduced in aorta from oleanolic acid-treated ApoE-/- and fluvastatin-treated ApoE-/- mice, compared to vehicle-treated ApoE-/-mice. Compared to vehicle and fluvastatin-treated ApoE-/- mice, aortic segments from wild type and oleanolic acid-treated ApoE-/-mice had a greater response to phenylephrine and less expression ofl inducible NO synthase. Actetylcholine relaxation was not improved in aortae from oleanolic acid or fluvastatin treated ApoE-/- mice. Oleanolic acid increases release of NO in isolated rat arteries and chronic administration of oleanolic acid has a pronounced anti-atherogenic effect in ApoE-/- mice, but the anti-atherogenic effect of oleanolic acid seems unrelated to endothelial release of NO.