Reading School of Pharmacy, School of Chemistry, Food and Pharmacy, The University of Reading, Reading, UK.
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 (BK ), ATP-sensitive potassium channels (K ) and possibly members of the K 7 family of voltage-activated potassium channels, resulting in hyperpolarisation and relaxation. ω-3 PUFA actions on BK 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.
高血压的特征通常是血管舒张功能受损，涉及多种血管舒张机制的功能障碍。ω-3 多不饱和脂肪酸（PUFA）、二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）可以降低血压和血管舒张。在内皮细胞中，DHA 和 EPA 可改善功能，包括增加一氧化氮的生物利用度。然而，动物研究表明，DHA 和 EPA 介导的血管舒张在去除内皮细胞后仍然存在，表明血管平滑肌细胞（VSMC）发挥作用。ω-3 PUFAs 对 VSMC 的血管舒张作用是通过打开大电导钙激活钾通道（BK）、ATP 敏感性钾通道（K）和可能的电压激活钾通道 K 家族成员介导的，导致超极化和松弛。ω-3 PUFA 对 BK 和电压门控离子通道的作用涉及静电相互作用，这些相互作用取决于多不饱和酰基尾部、这些双键的顺式几何形状和羧基头部的负电荷。这表明对 ω-3 PUFA 的结构操纵可以产生新的、有针对性的治疗靶点。
