Omega-3 polyunsaturated fatty acids and hypertension: a review of vasodilatory mechanisms of docosahexaenoic acid and eicosapentaenoic acid

Br J Pharmacol. 2021 Feb;178(4):860-877. doi: 10.1111/bph.15336. Epub 2021 Jan 4.


Hypertension is often characterised by impaired vasodilation involving dysfunction of multiple vasodilatory mechanisms. ω-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can reduce blood pressure and vasodilation. In the endothelium, DHA and EPA improve function including increased NO bioavailability. However, animal studies show that DHA- and EPA-mediated vasodilation persists after endothelial removal, indicating a role for vascular smooth muscle cells (VSMCs). The vasodilatory effects of ω-3 PUFAs on VSMCs are mediated via opening of large conductance calcium-activated potassium channels (BKCa ), ATP-sensitive potassium channels (KATP ) and possibly members of the Kv 7 family of voltage-activated potassium channels, resulting in hyperpolarisation and relaxation. ω-3 PUFA actions on BKCa and voltage-gated ion channels involve electrostatic interactions that are dependent on the polyunsaturated acyl tail, cis-geometry of these double bonds and negative charge of the carboxyl headgroup. This suggests structural manipulation of ω-3 PUFA could generate novel, targeted, therapeutic leads.

Keywords: DHA docosahexaenoic acid; EPA eicosapentaenoic acid; Nitric oxide; endothelium; hypertension; omega-3 polyunsaturated fatty acids (PUFA); vascular smooth muscle cells; vasodilation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Fatty Acids, Omega-3*
  • Hypertension*
  • Vasodilation


  • Fatty Acids, Omega-3
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid