178 20-HETE CONTRIBUTES TO THE BLOOD PRESSURE REDUCTION FOLLOWING OMEGA-3 FATTY ACID SUPPLEMENTATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract

Background and Objectives: Omega-3 fatty acids (n-3FA), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are protective against cardiovascular disease. n-3FA have multiple biological effects including benefits on blood pressure (BP). This study aimed to determine whether the reduction in 24-h ambulatory BP following supplementation with n-3 FA in patients with chronic kidney disease (1), was related to changes in the cytochrome P450 metabolite 20-HETE, a regulator of vascular tone and BP, and implicated in the pathogenesis of hypertension. Design and Methods: In a double-blind, placebo-controlled intervention, patients were randomized to either n-3FA (4 g), coenzyme Q10 (200 mg), both supplements, or control (4 g), daily for 8 weeks. All measures including 24-h ambulatory BP, plasma 20-HETE and F2-isoprostanes, and platelet fatty acids were recorded at baseline and after 8 weeks. Results: n-3FA, but not coenzyme Q10, reduced 24-h ambulatory BP by -3.3±0.7/-2.9 ± 0.5 mmHg (both P<0.0001). n-3 FA significantly reduced plasma 20-HETE by 28% (1217 ± 72 to 876 ± 69 pmol/L). Plasma 20-HETE levels were lower in females than males (P = 0.004) and significantly related to platelet EPA (b = -108.0, P = 0.013) and arachidonic acid (b = 20.7, P = 0.008), and plasma F2-isoprostanes (b = 0.7, P<0.0001). The fall in BP was positively associated with the reduction in plasma 20-HETE in regression analyses that adjusted for baseline BP (24-h SBP, P = 0.018 and 24-h DBP, P = 0.028). Conclusion: Reduced 20-HETE may play an important role in mediating the fall in BP following n-3 FA supplementation in patients with chronic kidney disease. Reference: Mori TA, et al. J Hypertension 2009;27:1863.