Background: Metabolism of arachidonic acid by cytochrome P450 ω-hydroxylase leads to the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) that regulates vascular function, sodium homeostasis and blood pressure (BP). Supplementation with n-3 fatty acids is known to alter arachidonic acid metabolism and reduce the formation of the lipid peroxidation products 2-isoprostanes">F2-isoprostanes, but the effect of n-3 fatty acids on 20-HETE has not been studied.
Method: We previously reported a significant effect of n-3 fatty acids but not coenzyme Q10 (CoQ) to reduce BP in a double-blind, placebo-controlled intervention, wherein patients with chronic kidney disease (CKD) were randomized to n-3 fatty acids (4 g), CoQ (200 mg), both supplements or control (4 g olive oil), daily for 8 weeks. This study examined the effect of n-3 fatty acids on plasma and urinary 20-HETE in the same study, as well as plasma and urinary 2-isoprostanes">F2-isoprostanes, and relate these to changes in BP.
Results: Seventy-four patients completed the 8-week intervention. n-3 fatty acids but not CoQ significantly reduced plasma 20-HETE (P = 0.001) and 2-isoprostanes">F2-isoprostanes (P < 0.001). In regression models adjusted for BP at baseline, postintervention plasma 20-HETE was a significant predictor of the fall in SBP (P < 0.0001) and DBP (P < 0.0001) after n-3 fatty acids.
Conclusion: This is the first report that n-3 fatty acid supplementation reduces plasma 20-HETE in humans and that this associates with reduced BP. These results provide a plausible mechanism for the reduction in BP observed in patients with CKD following n-3 fatty acid supplementation.
aSchool of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia
bDepartment of Nephrology and Transplantation, Royal Perth Hospital, Perth, Western Australia, Australia
Correspondence to Anne E. Barden, School of Medicine & Pharmacology, University of Western Australia, Level 4 MRF Building, Rear 50 Murray St, Perth, WA 6000, Australia. Tel: +618 9224 0272; fax: +618 9224 0246; e-mail: firstname.lastname@example.org
Abbreviations: 20-HETE, 20-hydroxyeicosatetraenoic acid; BHT, butylated hydroxytoluene; CKD, chronic kidney disease; CoQ, coenzyme Q10; DHA, docosahexaenoic acid; EETs, epoxyeicosatrienoic acids; EPA, eicosapentaenoic acid; GCMS, gas chromatography–mass spectrometry; GSH, reduced glutathione
Received 15 December, 2014
Revised 1 April, 2015
Accepted 1 April, 2015