EPA:DHA 6:1 prevents angiotensin II-induced hypertension and endothelial dysfunction in rats: role of NADPH oxidase- and COX-derived oxidative stress.

Eicosapentaenoic acid:docosahexaenoic acid (EPA:DHA) 6:1, an omega-3 polyunsaturated fatty acid formulation, has been shown to induce a sustained formation of endothelial nitric oxide (NO) synthase-derived NO, a major vasoprotective factor. This study examined whether chronic intake of EPA:DHA 6:1 prevents hypertension and endothelial dysfunction induced by angiotensin II (Ang II) in rats. Male Wister rats received orally corn oil or EPA:DHA 6:1 (500 mg kg-1 per day) before chronic infusion of Ang II (0.4 mg kg-1 per day). Systolic blood pressure was determined by tail cuff sphingomanometry, vascular reactivity using a myograph, oxidative stress using dihydroethidium and protein expression by immunofluorescence and western blot analysis. Ang II-induced hypertension was associated with reduced acetylcholine-induced relaxations of secondary branch mesenteric artery rings affecting the endothelium-dependent hyperpolarization (EDH)- and the NO-mediated relaxations, both of which were improved by the NADPH oxidase inhibitor VAS-2870. The Ang II treatment induced also endothelium-dependent contractile responses (EDCFs), which were abolished by the cyclooxygenase (COX) inhibitor indomethacin. An increased level of vascular oxidative stress and expression of NADPH oxidase subunits (p47phox and p22phox), COX-1 and COX-2, endothelial NO synthase and Ang II type 1 receptors were observed in the Ang II group, whereas SKCa and connexin 37 were downregulated. Intake of EPA:DHA 6:1 prevented the Ang II-induced hypertension and endothelial dysfunction by improving both the NO- and EDH-mediated relaxations, and by reducing EDCFs and the expression of target proteins. The present findings indicate that chronic intake of EPA:DHA 6:1 prevented the Ang II-induced hypertension and endothelial dysfunction in rats, most likely by preventing NADPH oxidase- and COX-derived oxidative stress.

Oxidation levels of North American over-the-counter n-3 (omega-3) supplements and the influence of supplement formulation and delivery form on evaluating oxidative safety.

The aim of the present study was to evaluate the oxidation status of North American n-3 (omega-3) PUFA nutritional supplements commercially available in Canada and evaluate the influence of product formulation and delivery form on oxidative safety. A total of 171 North American over-the-counter n-3 PUFA nutritional supplements were analysed for oxidation safety. Primary and secondary oxidation and total oxidation (TOTOX) were determined using the American Oil Chemists' Society (AOCS) procedures. Comparisons between supplements' final forms, oil source and n-3 PUFA concentration quartiles, as measures of product formulations and delivery forms, were compared using ANOVA. Of the products successfully tested, 50 % exceeded the voluntary recommended levels for markers of oxidation. Another 18 % of products were approaching the limits with 1-3 years before expiration. Encapsulated products without flavour additives had significantly lower secondary and TOTOX levels than bulk oils and flavoured products (P < 0·05). Children's products had significantly higher primary, secondary and TOTOX levels compared with all other products (P < 0·05). Markers of oxidation did not differ between oil sources (P > 0·05), with the exception of krill oil products having higher secondary oxidation levels than plant-based products (P > 0·05). Markers of oxidation did not differ between n-3 PUFA supplement concentration quartiles. Consumers may be at risk of exposure to higher levels of oxidative products. New regulatory mandates need to be introduced to ensure that all n-3 PUFA products, used as nutritional supplements, regardless of their formulation or delivery form, can be tested for oxidative safety and compliance.