Fig 6. A schematic showing potential mechanisms involved in n-3 PUFA-induced relaxation of rat mesenteric artery and aorta preconstricted with U46619.
Solid arrows represent pathways that have been previously investigated whereas dotted arrows represent hypothetical pathways based on our findings. In mesenteric arteries n-3 PUFAs enters the cytosol of the endothelium via diffusion from the plasma or release from the phospholipid bilayer via the activity of phospholipase A2 (PLA2); (1) EPA can be converted into EpETEs by CYP450, activating BKCa. IKCa may be potentially activated by (2) EpETEs, (3) EPA and (4) DHA. (5) Similar to EpETEs, EPA might also be involved in the direct activation of BKCa. (6) DHA directly activates BKCa (62). (7) Both n-3 PUFAs may enter the cytosol of VSMCs via diffusion or release from the phospholipid bilayer due to the activity of phospholipase A2 (PLA2) and directly activate BKCa. (8) CYP450 derived metabolites of EPA such as EpETEs may induce vasodilation through KCa independent mechanisms which could involve other potassium channels such as KATP.