Department of Health Sciences, University of Magna Graecia, 88100 Catanzaro, Italy.
Laboratory of General Physiology, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy.
Int J Mol Sci. 2023 Feb 15;24(4):3914. doi: 10.3390/ijms24043914.
N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate, mediate the slow component of excitatory neurotransmission in the central nervous system (CNS), and induce long-term changes in synaptic plasticity. NMDARs are non-selective cation channels that allow the influx of extracellular Na and Ca and control cellular activity via both membrane depolarization and an increase in intracellular Ca concentration. The distribution, structure, and role of neuronal NMDARs have been extensively investigated and it is now known that they also regulate crucial functions in the non-neuronal cellular component of the CNS, i.e., astrocytes and cerebrovascular endothelial cells. In addition, NMDARs are expressed in multiple peripheral organs, including heart and systemic and pulmonary circulations. Herein, we survey the most recent information available regarding the distribution and function of NMDARs within the cardiovascular system. We describe the involvement of NMDARs in the modulation of heart rate and cardiac rhythm, in the regulation of arterial blood pressure, in the regulation of cerebral blood flow, and in the blood-brain barrier (BBB) permeability. In parallel, we describe how enhanced NMDAR activity could promote ventricular arrhythmias, heart failure, pulmonary artery hypertension (PAH), and BBB dysfunction. Targeting NMDARs could represent an unexpected pharmacological strategy to reduce the growing burden of several life-threatening cardiovascular disorders.
N-甲基-D-天冬氨酸受体（NMDARs）是一种配体门控离子通道，被神经递质谷氨酸激活，介导中枢神经系统（CNS）中兴奋性神经传递的缓慢成分，并诱导突触可塑性的长期变化。NMDARs 是非选择性阳离子通道，允许细胞外 Na 和 Ca 的内流，并通过膜去极化和细胞内 Ca 浓度的增加来控制细胞活动。神经元 NMDAR 的分布、结构和作用已被广泛研究，现在已知它们还调节中枢神经系统中非神经元细胞成分（即星形胶质细胞和脑血管内皮细胞）的关键功能。此外，NMDARs 还在多个外周器官中表达，包括心脏和全身及肺循环。在此，我们调查了有关心血管系统中 NMDAR 分布和功能的最新信息。我们描述了 NMDARs 在心率和心脏节律调节、动脉血压调节、脑血流调节以及血脑屏障（BBB）通透性调节中的作用。同时，我们还描述了增强的 NMDAR 活性如何促进室性心律失常、心力衰竭、肺动脉高压（PAH）和 BBB 功能障碍。靶向 NMDARs 可能代表一种意想不到的药理学策略，可以降低几种危及生命的心血管疾病的日益增长的负担。
