Tone-dependent vascular responses to astrocyte-derived signals
Tone-dependent vascular responses to astrocyte-derived signals
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DOI：
10.1152/ajpheart.91451.2007
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发表时间：
2008-06-01
影响因子：
4.8
通讯作者：
Filosa, Jessica A.
中科院分区：
文献类型：
--
作者：
Blanco, Victor M.;Stern, Javier. E.;Filosa, Jessica A.
越来越多的研究支持星形胶质细胞对神经血管偶联的重要贡献，即，神经元活动的变化触发局部血流变化以满足神经元代谢需求的现象。然而，由于在星形胶质细胞刺激后在脑实质小动脉中观察到收缩和扩张，因此这些细胞对血管系统的具体影响仍不清楚。使用急性脑切片，我们提出的证据表明，大鼠皮层小动脉（血管张力）的收缩的具体程度是一个关键的决定因素的大小和极性的直径变化引起的信号与神经血管耦合。因此，细胞外K+浓度升高，代谢型谷氨酸受体（mGluR）的刺激，或11，12-epoxyeicosatrienoic acid的应用程序都引起了血管反应，受特定的静息小动脉张力。有趣的是，数据表明，血管反应的程度和/或极性受到以30和40%张力为中心的定界设定点的影响。此外，我们报告了在花生四烯酸途径的酶的抑制期间，在刺激mGluR时对小动脉直径发生不同的色调依赖性作用[即，磷脂酶A（2）、细胞色素P-450（β）ω-羟化酶、β-环氧合酶和环氧合酶-1]。我们的研究结果可能调和以前的证据，直接星形胶质细胞刺激引起血管收缩或血管舒张，也提出了新的概念，除了参与功能性充血，星形胶质细胞衍生的信号在调节血管张力的范围内发挥作用，扩张反应是最佳的。
A growing number of studies support an important contribution of astrocytes to neurovascular coupling, i.e., the phenomenon by which variations in neuronal activity trigger localized changes in blood flow that serve to match the metabolic demands of neurons. However, since both constriction and dilations have been observed in brain parenchymal arterioles upon astrocyte stimulation, the specific influences of these cells on the vasculature remain unclear. Using acute brain slices, we present evidence showing that the specific degree of constriction of rat cortical arterioles (vascular tone) is a key determinant of the magnitude and polarity of the diameter changes elicited by signals associated with neurovascular coupling. Thus elevation of extracellular K+ concentration, stimulation of metabotropic glutamate receptors (mGluR), or 11,12-epoxyeicosatrienoic acid application all elicited vascular responses that were affected by the particular resting arteriolar tone. Interestingly, the data suggest that the extent and/or polarity of the vascular responses are influenced by a delimited set point centered between 30 and 40% tone. In addition, we report that distinct, tone-dependent effects on arteriolar diameter occur upon stimulation of mGluR during inhibition of enzymes of the arachidonic acid pathway [i.e., phospholipase A(2), cytochrome P-450 (CYP) omega-hydroxylase, CYP epoxygenase, and cycloxygenase-1]. Our findings may reconcile previous evidence in which direct astrocytic stimulation elicited either vasoconstrictions or vasodilations and also suggest the novel concept that, in addition to participating in functional hyperemia, astrocyte-derived signals play a role in adjusting vascular tone to a range where dilator responses are optimal.