Recruitment of the Vascular Endothelium into Neurovascular Coupling

Abstract

In neurovascular coupling (NVC), neuronal activity in the brain leads to elevated local blood flow to satisfy the increased metabolic demands of the active tissue. The vascular endothelium has a major role in the modulation of blood flow, and here we explore the hypothesis that the endothelium has an important role in NVC.Brain slices were prepared from male C57 Bl/6 mice. Intraparenchymal arterioles were pre‐constricted with U46619 (125 nM). Neurons were depolarized with electrical field stimulation (EFS) to induce NVC and arteriolar dilation. In some experiments, the endothelium was loaded with di‐8‐ANEPPS (20 μM).EFS‐evoked arteriolar dilation was accompanied by endothelial hyperpolarization, as indicated by a 1.4% increase in the fluorescence ratio of di‐8‐ANEPPS (n=7). Blockade of I prostanoid receptors with 1 μM R01138452 had no effect on NVC (n=4). Blockade of neuronal nitric oxide synthase (NOS) with 7‐NI (100 μM) reduced the magnitude of vasodilation by 63% (n=7) with no effect on vessel tone (n=5). Blockade of both neuronal and endothelial NOS with L‐NNA (100 μM) caused a tonic constriction (17%, n=5) and reduced vasodilation by 89% (n=7). In the absence of U46619, L‐NNA constricted arterioles by 28% and reduced vasodilation by 90% (n=5).These data are consistent with the concept that the vascular endothelium is actively engaged during neurovascular coupling. Supported by NIH award P01 HL095489.