原发性醛固酮增多症（PA）是继发性高血压的常见原因之一，然而高醛固酮血症导致血压升高的神经机制尚存争议。我们据此提出，脑干孤束核和延髓头端腹外侧区的醛固酮信号系统功能异常，是导致PA高血压形成的重要神经机制。研究表明，TWIK-related acid-sensitive K通道敲除小鼠（TASK-/-）表现为高醛固酮血症和高血压，与人群中的特发性醛固酮增多症非常相似，是一个较理想的PA动物模型。本课题将利用TASK-/-小鼠模拟PA，观察TASK-/-小鼠动脉压力感受器反射是否异常；探讨孤束核和延髓头端腹外侧区醛固酮系统功能紊乱引起高血压的分子机制；筛选TASK-/-小鼠孤束核和延髓头端腹外侧区特征性MicroRNA，分析MicroRNA与醛固酮信号系统之间的关系。这些研究将有助于揭示PA高血压发生的分子神经机制，为临床上精准干预以及分子靶向药物的开发提供新的思路和线索。

Primary hyperaldosteronism (PA), the most common cause of secondary hypertension, is a direct consequence of autonomous aldosterone overproduction. However, the neurogenic mechanism underlying high plasma aldosterone-associated hypertension remains elusive. We hypothesize that dysfunction of aldosterone signaling in the nucleus tractus solitarii (NTS) and rostral ventrolateral medulla (RVLM) contributes to the development of hypertension in PA. It has been well documented that genetic deletion of TWIK-related acid-sensitive K channels (TASK-/-) in mice caused overproduction of aldosterone and hypertension, establishing an animal model of PA. This project is aimed to test whether dysfunction of arterial baroreflex occurs in TASK-/- mice, to explore the molecular mechanism of hypertension associated with aldosterone signaling in the NTS and RVLM, to compare neuroanatomical pattern of MicroRNAs in the NTS and RVLM and determine the specific MicroRNAs in TASK-/- mice. The results will be expected to reveal the molecular neurogenic mechanism of hyperaldosteronism-associated hypertension, and to provide novelty clues for precise clinical intervention and targeted drug development.