Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 178, Issue 4, Pages 860-877Publisher
WILEY
DOI: 10.1111/bph.15336
Keywords
hypertension; DHA docosahexaenoic acid; EPA eicosapentaenoic acid; omega‐ 3 polyunsaturated fatty acids (PUFA); vasodilation; endothelium; vascular smooth muscle cells; Nitric oxide
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Funding
- British Heart Foundation [PG/19/57/34568]
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Hypertension is characterised by impaired vasodilation, which can be improved by omega-3 polyunsaturated fatty acids such as DHA and EPA. These fatty acids also have vasodilatory effects on vascular smooth muscle cells (VSMCs) by opening potassium channels and possibly voltage-activated potassium channels, leading to hyperpolarisation and relaxation. Structural manipulation of omega-3 PUFAs may lead to novel therapeutic strategies.
Hypertension is often characterised by impaired vasodilation involving dysfunction of multiple vasodilatory mechanisms. omega-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 omega-3 PUFAs on VSMCs are mediated via opening of large conductance calcium-activated potassium channels (BKCa), ATP-sensitive potassium channels (K-ATP) and possibly members of the K(v)7 family of voltage-activated potassium channels, resulting in hyperpolarisation and relaxation. omega-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 omega-3 PUFA could generate novel, targeted, therapeutic leads.
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