Docosahexaenoic acid--induced vasorelaxation in hypertensive rats: mechanisms of action.
Docosahexaenoic acid--induced vasorelaxation in hypertensive rats: mechanisms of action.
复制标题
DOI：
10.1177/109980040000200202
复制
发表时间：
2000-10-01
影响因子：
2.5
通讯作者：
Engler, M M
中科院分区：
文献类型：
--
作者：
Engler, M B;Engler, M M
作者研究了omega-3脂肪酸二十二碳六烯（DHA, 22:6n-3）的血管松弛特性，以及内皮衍生的一氧化氮、前列腺素、K+通道开放和/或钙介导事件的调节可能参与。采用16-17周龄雄性自发性高血压大鼠（SHR）离体主动脉测量等长张力。在各种抑制剂和含钙溶液存在和不存在的情况下，在去甲肾上腺素（NE） （10(-6) mol/l）或高k + (80 mmol/l)溶液中收缩后，检测dha诱导的（1-100 mmol/l）松弛。DHA在NE和高k（+）诱导的收缩SHR主动脉环中均有显著的血管松弛作用，尽管DHA在高k（+）诱导的收缩环中松弛作用更大。在缺乏细胞外钙的情况下，DHA （5-30 μ mol/l）在不同条件下抑制ne诱导的初始期和持续期收缩成分。N - omega-硝基- l -精氨酸甲酯盐酸盐（100 μ mol/l）对一氧化氮合成的抑制作用对DHA松弛无影响；然而，吲哚美辛或硝苯地平对bb0或= 30 μ mol/l DHA有显著抑制作用。K+通道阻滞剂格列本脲对dha诱导的松弛也有抑制作用，但四乙基铵没有。这些结果表明DHA在SHR主动脉中的血管松弛作用不依赖于内皮源性一氧化氮；然而，当DHA浓度为>或= 30 μ mol/l时，激活atp敏感K+通道（KATP）的血管舒张性前列腺素可能参与其中。在较低浓度下，dha诱导的松弛似乎归因于血管平滑肌细胞内Ca2+释放和l型Ca2+通道的调节。在这种高血压模型中，DHA的血管松弛特性可能在一定程度上有助于膳食鱼油的降血压作用。
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.