Barden Anne E, Burke Valerie, Mas Emilie, Beilin Lawrence J, Puddey Ian B, Watts Gerald F, Irish Ashley B, Mori Trevor A
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.
J Hypertens. 2015 Sep;33(9):1947-53. doi: 10.1097/HJH.0000000000000621.
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 F2-isoprostanes, but the effect of n-3 fatty acids on 20-HETE has not been studied.
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 F2-isoprostanes, and relate these to changes in BP.
Seventy-four patients completed the 8-week intervention. n-3 fatty acids but not CoQ significantly reduced plasma 20-HETE (P = 0.001) and 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.
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.
细胞色素P450 ω-羟化酶对花生四烯酸的代谢导致20-羟基二十碳四烯酸（20-HETE）的形成，其可调节血管功能、钠稳态和血压（BP）。已知补充n-3脂肪酸可改变花生四烯酸代谢并减少脂质过氧化产物F2-异前列腺素的形成，但n-3脂肪酸对20-HETE的影响尚未得到研究。
我们之前报道了在一项双盲、安慰剂对照干预中，n-3脂肪酸而非辅酶Q10（CoQ）对降低血压有显著作用，其中慢性肾脏病（CKD）患者被随机分为每日服用n-3脂肪酸（4克）、CoQ（200毫克）、两种补充剂或对照（4克橄榄油），持续8周。本研究在同一研究中检测了n-3脂肪酸对血浆和尿液中20-HETE以及血浆和尿液中F2-异前列腺素的影响，并将这些与血压变化相关联。
74名患者完成了为期8周的干预。n-3脂肪酸而非CoQ显著降低了血浆20-HETE（P = 0.001）和F2-异前列腺素（P < 0.001）。在针对基线血压进行调整的回归模型中，干预后血浆20-HETE是n-3脂肪酸治疗后收缩压（SBP）下降（P < 0.ooo1）和舒张压（DBP）下降（P < 0.0001）的显著预测指标。
这是首份关于补充n-3脂肪酸可降低人体血浆20-HETE且这与血压降低相关的报告。这些结果为CKD患者补充n-3脂肪酸后血压降低提供了一种合理机制。
