Ultrasound stimulates formation and release of vasoactive compounds in brain endothelial cells
Ultrasound stimulates formation and release of vasoactive compounds in brain endothelial cells
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DOI：
10.1152/ajpheart.00690.2014
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发表时间：
2015-08-15
影响因子：
4.8
通讯作者：
Kaul, Sanjiv
中科院分区：
文献类型：
--
作者：
Davis, Catherine M.;Ammi, Azzdine Y.;Kaul, Sanjiv
超声治疗可改善中风结果。据推测，这种益处主要来自超声介导的溶栓。我们假设超声波对中风的治疗作用可能部分是由有益的血管活性物质的释放介导的。因此，我们在体外研究了超声对原代脑内皮细胞中细胞色素 P-450、脂氧合酶和花生四烯酸环加氧酶代谢物水平以及腺苷释放和内皮一氧化氮合酶 (eNOS) 磷酸化的影响。脑内皮细胞暴露于 1.05 MHz 超声，峰值稀疏声压振幅为 0.35、0.55、0.90 和 1.30 MPa。超声暴露后测量环氧二十碳三烯酸 (EET)、羟基二十碳四烯酸 (HETE)、PGE(2)、腺苷、硝酸盐/亚硝酸盐和 eNOS 磷酸化。 8,9-EET、11,12-EET 和 14,15-EET 水平分别增加 230 +/- 28%、240 +/- 30% 和 246 +/- 31% (P < 0.05)，而 5-HETE 和 15-HETE 水平降低至 24 +/- 14% 和 10 +/- 3% (P < 0.05），分别与未暴露于超声的细胞相比。 PGE(2) 水平降低至对照的 56 +/- 14%。与未刺激的细胞相比，超声波照射后腺苷增加了六倍以上（1.36 +/- 0.22 vs. 0.37 +/- 0.10 ng/ml，P < 0.05），硝酸盐/亚硝酸盐低于定量水平，并且 eNOS 磷酸化没有显着改变。我们的结果表明，超声波可以通过增加血管舒张化合物的产生并抑制血管收缩剂的产生来增强中风期间的组织灌注。这种调节支持超声治疗在中风中的有益作用，而与其对闭塞血栓的影响无关。
Stroke outcome is improved by therapeutic ultrasound. This benefit is presumed to be principally from ultrasound-mediated thrombolysis. We hypothesized that the therapeutic benefit of ultrasound in stroke may, in part, be mediated by the release of beneficial vasoactive substances. Accordingly, we investigated the effect of ultrasound on levels of cytochrome P-450, lipoxygenase, and cyclooxygenase metabolites of arachidonic acid as well as adenosine release and endothelial nitric oxide synthase (eNOS) phosphorylation in primary brain endothelial cells in vitro. Brain endothelial cells were exposed to 1.05-MHz ultrasound at peak rarefactional acoustic pressure amplitudes of 0.35, 0.55, 0.90, and 1.30 MPa. Epoxyeicosatrienoic acids (EETs), hydroxyeicosatetraenoic acids (HETEs), PGE(2), adenosine, nitrate/nitrite, and eNOS phosphorylation were measured after ultrasound exposure. Levels of 8,9-EET, 11,12-EET, and 14,15-EET increased by 230 +/- 28%, 240 +/- 30%, and 246 +/- 31% (P < 0.05), respectively, whereas 5-HETE and 15-HETE levels were reduced to 24 +/- 14% and 10 +/- 3% (P < 0.05), respectively, compared with cells not exposed to ultrasound. PGE(2) levels were reduced to 56 +/- 14% of control. Adenosine increased more than sixfold after ultrasound exposure compared with unstimulated cells (1.36 +/- 0.22 vs. 0.37 +/- 0.10 ng/ml, P < 0.05), nitrate/nitrite was below levels of quantification, and eNOS phosphorylation was not altered significantly. Our results suggest that ultrasound may enhance tissue perfusion during stroke by augmenting the generation of vasodilator compounds and inhibiting that of vasoconstrictors. Such regulation supports a beneficial role for therapeutic ultrasound in stroke independent of its effect on the occlusive thrombus.