NADH augments blood flow in physiologically activated retina and visual cortex
NADH augments blood flow in physiologically activated retina and visual cortex
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DOI：
10.1073/pnas.0307458100
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发表时间：
2004-01-13
影响因子：
11.1
通讯作者：
Williamson, JR
中科院分区：
文献类型：
--
作者：
Ido, Y;Chang, K;Williamson, JR
在视觉刺激下增加视网膜和视觉皮层血流量的机制尚不清楚。我们测试了这样一种假设，即通过增加能量代谢引起的从葡萄糖到胞质游离NAD+的电子和质子转移增加，将其还原为NADH，为氧化还原信号通路提供燃料，从而增加流量。乳酸脱氢酶建立的胞质内自由NADH/NAD（+）和乳酸/丙酮酸比值的接近平衡预测，从注射的乳酸中转移到NAD+的额外电子和质子将增加受刺激的视网膜和皮层中升高的血流量，而从NADH转移到注射的丙酮酸的电子和质子将减弱升高的血流量。这些预测在大鼠身上得到了验证。一氧化氮合酶的抑制也阻止了刺激引起的血流增加。这些发现支持细胞质内游离NADH在促进(NO)- n -增加的信号级联中的重要作用。产生，它增加了光刺激视网膜和视觉皮层的血液流动。
The mechanism(s) that increase retinal and visual cortex blood flows in response to visual stimulation are poorly understood. We tested the hypothesis that increased transfer of electrons and protons from glucose to cytosolic free NAD+, reducing it to NADH, evoked by increased energy metabolism, fuels redox-signaling pathways that augment flow. The near-equilibrium between free cytosolic NADH/NAD(+) and lactate/pyruvate ratios established by lactate dehydrogenase predicts that transfer of additional electrons and protons from injected lactate to NAD+ will augment the elevated blood flows in stimulated retina and cortex, whereas transfer of electrons and protons from NADH to injected pyruvate will attenuate the elevated flows. These predictions were tested and confirmed in rats. Increased flows evoked by stimulation also were prevented by inhibition of nitric oxide synthase. These findings support an important role for cytosolic free NADH in fueling a signaling cascade that increases (NO)-N-. production, which augments blood flow in photostimulated retina and visual cortex.