The authors investigated the vasorelaxant properties of the omega-3 fatty acid, docosahexaenoic (DHA, 22:6n-3), and the possible involvement of endothelium- derived nitric oxide, prostanoids, opening of K+ channels, and/or modulation of calcium-mediated events. Isolated aorta from male spontaneously hypertensive rats (SHR) (age 16-17 weeks) were used to measure isometric tension. DHA-induced (1-100 mol/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 various inhibitors and calcium-containing solution. DHA acid induced a significant vasorelaxant effect in both NE and high-K+-induced contracted SHR aortic rings, although DHA relaxations were greater in high-K+- induced contracted rings. In the absence of extracellular calcium, DHA (5-30 mol/l) inhibited the initial phasic and sustained components of NE-induced contraction under different conditions. Inhibition of nitric oxide synthesis by N-nitro-L-arginine methyl ester hydrochloride (100 mol/l)
had no effect on DHA relaxations; however, indomethacin or nifedipine caused significant inhibition at 30 mol/l DHA. The K+ channel blocker, glibenclamide, but not tetraethyl-ammonium, also had an inhibitory effect on DHA- induced relaxation. These results indicate that DHA?s vasorelaxant actions in SHR aorta are independent of endothelium-derived nitric oxide; however, at DHA concentrations 30 mol/l, vasodilatory prostanoids that activate ATP sensitive K+ channels (KATP) may be involved. At lower concentrations, DHA-induced relaxation appears to be attributed to modulation of intracellular Ca2+ release and L-type Ca2+ channels in vascular smooth muscle cells. The vasorelaxant properties of DHA may contribute, in part, to the blood pressure?lowering effect of dietary fish oil in this hypertensive model. |