Arachidonate dilates basilar artery by lipoxygenase-dependent mechanism and activation of K+ channels
Arachidonate dilates basilar artery by lipoxygenase-dependent mechanism and activation of K+ channels
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DOI：
10.1152/ajpregu.2001.281.1.r246
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发表时间：
2001-07-01
影响因子：
2.8
通讯作者：
Weintraub, NL
中科院分区：
文献类型：
--
作者：
Faraci, FM;Sobey, CG;Weintraub, NL
花生四烯酸引起的脑小动脉扩张依赖于环氧合酶的活性。在这项研究中，我们研究了花生四烯酸介导基底动脉扩张的机制。使用麻醉大鼠的颅窗测量基底动脉的直径（基线直径= 216 +/- 7 μ m）（平均值+/- SE）。花生四烯酸（10和100 μ M）产生浓度依赖性血管舒张，吲哚美辛（10 mg/kg iv）或N-G-硝基-L-精氨酸（100 μ M）不能抑制这种舒张，但黄芩素（10 μ M）或去甲二氢愈创木酸（NDGA; 10 mM）（脂氧合酶途径的抑制剂）能显著抑制这种舒张。基底动脉扩张也明显抑制四乙基铵离子（TEA; 1 mM）或伊比利亚毒素（50 nM），钙依赖性钾通道的抑制剂。例如，在不存在和存在伊比利亚毒素的情况下，10 mM花生四烯酸盐分别使基底动脉扩张19 +/-7和1 +/-1%。膜电位的测量表明，花生四烯酸产生的基底动脉被完全阻断TEA的超极化。用[H-3]花生四烯酸孵育，然后进行反相和手性HPLC，表明基底动脉产生相对少量的前列腺素类，但产生大量的12（S）羟基二十碳四烯酸（12-S-HETE），这是一种脂氧合酶产物。黄芩素和NDGA均能抑制12-HETE的产生。这些发现表明，花生四烯酸引起的基底动脉扩张是由脂氧合酶途径的产物介导的，并伴有钙依赖性钾通道的激活和血管肌肉的超极化。
Dilatation of cerebral arterioles in response to arachidonic acid is dependent on activity of cyclooxygenase. In this study, we examined mechanisms that mediate dilatation of the basilar artery in response to arachidonate. Diameter of the basilar artery (baseline diameter = 216 +/- 7 mum) (means +/- SE) was measured using a cranial window in anesthetized rats. Arachidonic acid (10 and 100 muM) produced concentration-dependent vasodilatation that was not inhibited by indomethacin (10 mg/kg iv) or N-G-nitro-L-arginine (100 muM) but was inhibited markedly by baicalein (10 muM) or nordihydroguaiaretic acid (NDGA; 10 mM), inhibitors of the lipoxygenase pathway. Dilatation of the basilar artery was also inhibited markedly by tetraethylammonium ion (TEA; 1 mM) or iberiotoxin (50 nM), inhibitors of calcium-dependent potassium channels. For example, 10 mM arachidonate dilated the basilar artery by 19 +/- 7 and 1 +/- 1% in the absence and presence of iberiotoxin, respectively. Measurements of membrane potential indicated that arachidonate produced hyperpolarization of the basilar artery that was blocked completely by TEA. Incubation with [H-3] arachidonic acid followed by reverse-phase and chiral HPLC indicated that the basilar artery produces relatively small quantities of prostanoids but large quantities of 12(S) hydroxyeicosatetraenoic acid (12-S-HETE), a lipoxygenase product. Moreover, the production of 12-HETE was inhibited by baicalein or NDGA. These findings suggest that dilatation of the basilar artery in response to arachidonate is mediated by a product(s) of the lipoxygenase pathway, with activation of calcium-dependent potassium channels and hyperpolarization of vascular muscle.