National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
Brain Res. 2011 Aug 17;1407:62-8. doi: 10.1016/j.brainres.2011.06.045. Epub 2011 Jun 29.
Nitric oxide (NO), a potent vasodilator and nontraditional neurotransmitter, is an important mediator of the changes in cerebral blood flow (CBF) associated with increased neuronal activity (neurovascular coupling). In the present work, we investigated the role of NO and of its newly recognized precursor, nitrite, in neurovascular coupling using a well-established rat model of somatosensory stimulation. Biological synthesis of NO of neuronal origin was inhibited pharmacologically. Following the initial uncoupling of neuronal and hemodynamic responses to somatosensory stimulation, the NO donor sodium nitroprusside, added within the range of physiological concentrations, significantly increased, but did not fully restore the functional CBF response. In contrast, nitrite at its physiological concentration fully recovered neurovascular coupling to its original magnitude. The magnitude of the effect is, however, dose-dependent. Sub-physiological concentrations of nitrite were not enough to entirely restore neurovascular coupling and supra-physiological concentrations acted more as a local vasodilator that changed resting CBF and interfered with the functional CBF response. These results suggest that nitrite can be efficiently converted into NO and utilized to support normal cerebrovascular physiology.
一氧化氮（NO）是一种强效的血管舒张剂和非传统神经递质，是与神经元活动增加相关的脑血流（CBF）变化的重要介质（神经血管耦联）。在本工作中，我们使用已建立的感觉刺激大鼠模型研究了 NO 及其新发现的前体亚硝酸盐在神经血管耦联中的作用。通过药理学抑制神经元来源的 NO 的生物合成。在感觉刺激引起的神经元和血液动力学反应最初脱耦联后，加入生理浓度范围内的一氧化氮供体硝普钠可显著增加，但不能完全恢复功能性 CBF 反应。相比之下，生理浓度的亚硝酸盐完全恢复了神经血管耦联到原来的幅度。然而，该作用的幅度是剂量依赖性的。低于生理浓度的亚硝酸盐不足以完全恢复神经血管耦联，而高于生理浓度的亚硝酸盐更像是一种局部血管扩张剂，改变静息 CBF 并干扰功能性 CBF 反应。这些结果表明，亚硝酸盐可以有效地转化为 NO 并用于支持正常的脑血管生理学。
