Docosahexaenoic acid-induced vasorelaxation in hypertensive rats: Modulation of calcium-mediated events

Dietary fish oil, rich in the omega-3 fatty acids, docosahexaenoic (DHA, 22:6n-3) and eicosapentaenoic (EPA, 20:5n-3), is associated with a blood pressure lowering effect which may, in part, be related to the vasorelaxant properties of these two fatty acids. The relaxant effects of DHA in male SHR (age 16-17 wks) isolated aorta were investigated with possible involvement of endothelium-derived nitric oxide (EDNO), prostanoids/cyclooxygenated products, opening of K⁺-channels, and/or modulation of calcium-mediated events. Isometric tension was measured. DHA-induced (1-100 μmol/l) relaxation was examined following contraction to norepinephrine (NE, 10^-6 mol/l) or high K⁺ (80 mmol/l) solution in the presence and absence of N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 μmol/l) and indomethacin (10 μmol/l). The effect of potassium (K⁺)-channel blockers, tetraethylammonium (TEA, 1 mmol/l) and glibenclamide (10 μmol/l), on DHA-induced (100 μmol/l) relaxation was also determined. Calcium-free solution with ethylene glycol-bis (β-aminoethylether)-N, N′-tetraacetic acid (EGTA, 2 mmol/l) was used to evaluate the possible modulation of intracellular calcium by DHA. A nonsetective vasorelaxant effect by DHA was seen in both NE- and high-K⁺-induced contracted SHR aortic rings pretreated with L-NAME and indomethacin. Use of these inhibitors enhanced DHA-induced (1-100 μmol/l) relaxations in NE-contracted rings. In calcium-free EGTA containing solution, DHA inhibited the initial phasic and sustained component of NE-induced contraction under different conditions. K⁺-channel blockers had no effect on DHA-induced relaxation. Thus, the vasorelaxant effects of DHA in SHR aorta are independent of vasodilatory cydooxygenated products, EDNO, and K⁺-channel opening but appear related to calcium-mediated events.