Docosahexaenoic acid--induced vasorelaxation in hypertensive rats: mechanisms of action.
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 mumol/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 mumol/l) inhibited the initial phasic and sustained components of NE-induced contraction under different conditions. Inhibition of nitric oxide synthesis by N omega-nitro-L-arginine methyl ester hydrochloride (100 mumol/l) had no effect on DHA relaxations; however, indomethacin or nifedipine caused significant inhibition at > or = 30 mumol/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 > or = 30 mumol/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.
Engler
M B
MB
Department of Physiological Nursing, Laboratory of Cardiovascular Physiology, University of California, San Francisco, USA.
Engler
M M
MM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D014664:Vasodilation / Q000187:drug effects
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D015221:Potassium Channels; D004281:Docosahexaenoic Acids; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine