高盐和应激致室旁核神经激素兴奋引发血管功能异常和高血压的机制

高盐饮食和应激是高血压的重要危险因素。血管稳态失衡与重构是高血压的主要病理基础。本课题拟研究高盐饮食和应激是否引起下丘脑室旁核神经激素兴奋，进而引发血管稳态失衡与重构和高血压并探讨其机制。经双侧室旁核给予应激性高血压和自发性高血压大鼠促肾上腺皮质激素释放激素(CRH)阻断剂4周，经双侧室旁核给予盐敏感性高血压大鼠肾素-血管紧张素系统(RAS)组分、炎性细胞因子(PIC)、活性氧簇(ROS)、去甲肾上腺素受体、谷氨酸受体阻断剂或γ-氨基丁酸受体激动剂4周，植入式无线遥测系统记录血压和肾交感神经活动，检测室旁核RAS、PIC、CRH、ROS和神经递质的变化，观察血管活性物质及血管稳态与重构的指标变化，探讨高盐和应激引起室旁核神经激素兴奋，进而导致交感神经活动增强、血管稳态失衡与血压升高的机制。本课题探讨血管稳态失衡与重构和高血压的中枢机制，为血管稳态失衡与重构及高血压的防治寻求早期干预的靶点。

High-salt diet and chronic stress are important risk factors of hypertension. Imbalance of vascular homeostasis and vascular remodeling contribute to the pathogenesis of hypertension. This study will explore whether high-salt diet and chronic stress-induced imbalance of vascular homeostasis and vascular remodeling are mediated by the neurohormonal excitation (NHE) in the hypothalamic paraventricular nucleus (PVN). Stress-induced hypertensive rats and spontaneously hypertensive rats (SHR) will be treated for 4 weeks with bilateral PVN infusion of corticotrophin releasing hormone (CRH) blocker, and Dahl salt sensitive rats will be treated for 4 weeks with bilateral PVN infusion of the blockers of renin-angiotensin system (RAS) components, proinflammatory cytokines (PIC) or reactive oxygen species (ROS), the antagonist of glutamate (Glu) or norepinephrine (NE) receptor, the agonist of gamma-aminobutyric acid (GABA) receptor, or vehicle. The mean arterial pressure, renal sympathetic nerve activity, the levels of vasoactive substancesin blood, and vascular function will be measured. The levels of the neurotransmitters, RAS, PIC, CRH and ROS in the PVN of these rats will also be measured. This study will determine whether high salt- and stress-induced imbalance of vascular homeostasis, vascular remodeling and hypertension are mediated by the neurohormonal excitation in the PVN. This study will explore the central mechanism of imbalance of vascular homeostasis, vascular remodeling and hypertension. The successful completion of this study will expand our knowledge about the PVN mechanisms contributing to the pathogenesis of imbalance of vascular homeostasis, vascular remodeling and hypertension. This study will ultimately lead to new and effective strategies to treat hypertension and so have important clinical implications.