下丘脑室旁核和延髓头端腹外侧区神经递质在高血压中的作用

交感神经兴奋是高血压发生发展的重要机制，脑内交感前神经元主要集中于下丘脑室旁核(PVN)和延髓头端腹外侧区(RVLM)。本课题拟研究高血压时PVN和RVLM区神经递质改变是否影响交感神经活动和血压变化并探讨其机制。血管紧张素II诱导的高血压大鼠经双侧室旁核连续4周分别给予肾素-血管紧张素系统(RAS)组分、炎性细胞因子(PIC)、活性氧簇(ROS)阻断剂，高血压大鼠和正常大鼠经双侧室旁核连续4周给予神经递质(去甲肾上腺素、谷氨酸和γ-氨基丁酸)阻断剂或激动剂，植入式无线遥测系统同时记录血压和肾交感神经活动，检测血浆、PVN和RVLM区RAS、PIC、ROS和神经递质及其限速酶等指标，以观察PVN和RVLM区神经递质与RAS、PIC及ROS的相互作用及其对交感神经活动和血压的影响。通过神经元示踪技术标记PVN和RVLM区交感前神经元的分布及其投射路径。本课题将为高血压的研究和治疗提供新思路。

The sympathoexcitation plays vital roles in the pathogenesis of hypertension. Presympathetic neurons mainly distribute in the hypothalamic paraventricular nucleus (PVN) and the rostral ventrolateral medulla (RVLM). This study will explore whether angiotensin II (ANG II)-induced sympathoexcitation and hypertensive response are mediated by the neurotransmitters in the PVN and the RVLM. Hypertensive rats will be made by subcutaneous infusions of ANG II. Rats will be treated for 4 weeks through bilateral PVN infusion with the blocker of renin-angiotensin system (RAS), proinflammatory cytokines (PIC), reactive oxygen species (ROS), the agonist or the antagonist of the neurotransmitter (glutamate, norepinephrine (NE) or gamma-aminobutyric acid (GABA)), or vehicle. The mean arterial pressure, renal sympathetic nerve activity, the levels of the neurotransmitters, RAS, PIC and ROS in the PVN and the RVLM of these rats will be measured. This study will determine whether the interaction between RAS and PIC modulates the neurotransmitters in the PVN and the RVLM, and whether these neurotransmitters affect the RAS, PIC and ROS, and contribute to angiotensin II-induced sympathoexcitation and hypertensive response. The flurogold will be microinjected into the intermediolateral cell column (IML) to prelabel presympathetic projection pathways. The successful completion of the study will expand our knowledge regarding brain mechanisms of hypertension and ultimately lead to new and effective strategies to treat hypertension.