Omega-3 Fatty Acids in Arterial Hypertension: Is There Any Good News?

Abstract

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including alpha-linolenic acid (ALA) and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are "essential" fatty acids mainly obtained from diet sources comprising plant oils, marine blue fish, and commercially available fish oil supplements. Many epidemiological and retrospective studies suggested that ω-3 PUFA consumption decreases the risk of cardiovascular disease, but results of early intervention trials have not consistently confirmed this effect. In recent years, some large-scale randomized controlled trials have shed new light on the potential role of ω-3 PUFAs, particularly high-dose EPA-only formulations, in cardiovascular prevention, making them an attractive tool for the treatment of "residual" cardiovascular risk. ω-3 PUFAs' beneficial effects on cardiovascular outcomes go far beyond the reduction in triglyceride levels and are thought to be mediated by their broadly documented "pleiotropic" actions, most of which are directed to vascular protection. A considerable number of clinical studies and meta-analyses suggest the beneficial effects of ω-3 PUFAs in the regulation of blood pressure in hypertensive and normotensive subjects. These effects occur mostly through regulation of the vascular tone that could be mediated by both endothelium-dependent and independent mechanisms. In this narrative review, we summarize the results of both experimental and clinical studies that evaluated the effect of ω-3 PUFAs on blood pressure, highlighting the mechanisms of their action on the vascular system and their possible impact on hypertension, hypertension-related vascular damage, and, ultimately, cardiovascular outcomes.

Keywords: alpha-linoleic acid (ALA); arterial stiffness; docosahexaenoic acid (DHA); eicosapentaenoic acid (EPA); endothelial dysfunction; hypertension; linoleic acid (LA); omega-3 polyunsaturated fatty acids (ω-3 PUFAs); oxylipins; primary prevention; residual cardiovascular risk; secondary prevention.

Figure 1

Structure of polyunsaturated fatty acids and their formation from parental molecules.

Figure 2

Schematic representation of actions of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on cell membranes and intracellular signaling and their relevance for perivascular adipocytes and vascular cell functions. EEQ, epoxyeicosatetraenoic acid; NADPH, nicotinamide adenine dinucleotide; SOD, superoxide dismutase; XO, xanthine oxidase; PVAT, perivascular adipose tissue; ADRF, adventitium-derived relaxing factor; COX, cyclooxygenase; PGI2, prostacyclin; NO, nitric oxide; eNOS, endothelial nitric oxide synthase; ADMA, asymmetric dimethylarginine; EET, epoxyeicosatrienoic acid; endothelium-derived hyperpolarizing factor; BKCa, large-conductance voltage- and calcium-activated potassium channel; TRPV-4, transient receptor potential vanilloid-4; TRPC1/5, transient receptor potential cation.

Figure 3

Changes in blood pressure levels as measured by noninvasive ambulatory blood pressure monitoring (ABPM) in hypertensive patients who ate 3 weekly meals of trout rich in polyunsaturated fatty acids for 6 months. Changes are represented according to change (↑ increase; ↓ decrease) in erythrocyte cell membrane polyunsaturated to saturated fatty acid ratio (PUFA/SFA). Only hypertensive patients with an increased PUFA/SFA had significant 24-hour and nighttime blood pressure reduction (adapted from ref. [93]). * p < 0.05.