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DOI: 10.1177/109980040000200202 Docosahexaenoic Acid-Induced Vasorelaxation in Hypertensive Rats: Mechanisms of Action
Department of Physiological Nursing, Laboratory of Cardiovascular Physiology, University of California, San Francisco. 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 AT Psensitive 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.
Key Words: Docosahexaenoic • omega-3 fatty acid • hypertension • relaxation • rat aorta • nitric oxide • calcium • cyclooxygenase • potassium channels • L-type calcium channels
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