HYPERHOMOCYST(E)INEMIA INDUCED BY METHIONINE LOADING

甲硫氨酸负荷引起的同型半胱氨酸（E）血症

• 批准号: 7377102
• 负责人: WILLIAM G HAYNES
• 金额: $ 1.29万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377102
• 关键词: HYPERHOMOCYST; INEMIA; INDUCED; METHIONINE; LOADING

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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。已发现高同型半胱氨酸血症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，其作用机制尚不清楚。 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 受体刺激可能引起神经毒性。同型半胱氨酸具有神经毒性作用，可诱导实验动物癫痫发作和行为改变，这是由于 NMDA 受体刺激以及产生自由基所致。它还具有血管效应，通过激活神经嵴衍生的血管平滑肌细胞 (VSMC) 中的 NMDA 相关受体，导致 VSMC 中 DNA 合成增加和细胞增殖。脑干和脊髓中的NMDA受体和兴奋性神经递质在交感神经活动的维持和调节以及中枢心血管调节中发挥着重要作用。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、反射性交感心脏效应和躯体交感反射。考虑到同型半胱氨酸对 NMDA 受体的刺激，以及 NMDA 受体对交感神经流出调节的重要性，高同型半胱氨酸血症可能通过 NMDA 受体激活增加交感神经活动。因此，本研究将检验以下假设：甲硫氨酸负荷引起的实验性高同型半胱氨酸血症会增加健康人的肌肉交感神经活动。将使用显微神经造影技术通过直接神经内记录来评估肌肉交感神经活动。