HYPERHOMOCYST(E)INEMIA INDUCED BY METHIONINE LOADING

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。高同泡血症已被发现与早发性动脉和静脉血栓形成有关，并且是冠状动脉疾病和脑血管疾病的危险因素。然而，它的作用机制尚不清楚。n -甲基d -天冬氨酸（NMDA）受体是脑干、脊髓和自主神经系统中兴奋性神经递质的受体。NMDA受体刺激可引起神经毒性。同胞素(e)ine具有神经毒性作用，在实验动物中引起癫痫发作和行为改变，这是由于NMDA受体受到刺激以及产生自由基。它还具有血管效应，通过激活神经冠源性血管平滑肌细胞（VSMC）中的nmda相关受体，导致神经冠源性血管平滑肌细胞（VSMC）中DNA合成和细胞增殖增加。脑干和脊髓中的NMDA受体和兴奋性神经递质在维持和调节交感神经活动和中枢心血管调节中起重要作用。它们介导脑桥和延髓的血管加压反应、延髓和脊髓的压力反射功能、交感心脏反射效应和体交感反射。考虑到NMDA受体受同型囊(e)线的刺激，以及NMDA受体在调节交感神经外流中的重要性，高同型囊(e)血症可能通过NMDA受体激活而增加交感神经活动。因此，本研究将验证由蛋氨酸负荷引起的实验性高同胞血症(e)增加健康人肌肉交感神经活动的假设。肌肉交感神经活动将通过使用微神经摄影技术的直接神经内记录来评估。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hyperhomocyst(e)inemia has been found to be associated with early onset arterial and venous thrombosis, and as a risk factor for coronary artery disease and cerebrovascular disease. However, the mechanisms through which it acts is unclear. N-Methyl D-aspartate (NMDA) receptors are receptors for excitatory neurotransmitters in the brain stem, spinal cord and autonomic nervous system. NMDA receptor stimulation may cause neurotoxicity. Homocyst(e)ine has neurotoxic actions, inducing seizures and behavioral changes in experimental animals, which are due to NMDA receptor stimulation as well as by producing free radicals. It also has vascular effects, causing increased DNA synthesis and cell proliferation in neural crest-derived vascular smooth muscle cells (VSMC), through activation of a NMDA-related receptor in VSMC. NMDA receptors and excitatory neurotransmitters in the brain stem and spinal cord play an important role in the maintenance and regulation of sympathetic nerve activity and central cardiovascular regulation. They mediate vasopressor responses of the pons and medulla, baroreflex functions of the medulla and spinal cord, reflex sympathetic heart effects and somatosympathetic reflexes. Considering the stimulation by homocyst(e)ine of NMDA receptors, and the importance of NMDA receptors on regulation of sympathetic outflow, it is possible that hyperhomocyst(e)inemia may increase sympathetic nerve activity through NMDA receptor activation. This study will, therefore, test the hypothesis that experimental hyperhomocyst(e)inemia, induced by methionine loading, increases muscle sympathetic nerve activity in healthy humans. Muscle sympathetic nerve activity will be assessed by direct intraneural recordings using microneurography techniques.