肾脏PRR通过促进肾脏局部醛固酮的分泌调控钠钾平衡及血压稳态

水盐代谢絮乱是引起高血压的主要危险因素之一。低钠高钾饮食现已被推荐为高血压等心血管疾病的健康饮食方式。研究表明肾脏肾素原受体(PRR)在钠钾平衡及血压调控中发挥重要作用。预实验结果表明，肾小管特异性PRR或醛固酮合成酶CYP11B2敲除小鼠，在低盐饮食下均表现尿钠排泄增多，在高钾饮食下均表现尿钾排泄减少及高钾血症，两者均伴随尿醛固酮排泄减少。据此我们推测：肾脏PRR通过促进肾内醛固酮的产生来增强肾脏对钠的重吸收作用及尿钾排泄。因此，本项目将利用肾小管特异性PRR及CYP11B2基因诱导性敲除小鼠及集合管特异性肾素基因敲除小鼠阐明肾脏PRR-CYP11B2-醛固酮信号在机体调节钠钾平衡及血压稳态中的重要作用，为临床肾素-血管紧张素-醛固酮系统抑制剂的使用提供新的视点和策略。

Water-salt metabolism disorder is one of the main risk factors for the development of hypertension. Low-Na+ high-K+ diet has been recommended as a healthy diet for cardiovascular diseases such as hypertension. Several studies have shown that renal prorenin receptor (PRR) plays an important role in Na+ and K+ balance and blood pressure regulation. The results from our preliminary studies showed renal tubule-specific PRR or aldosterone synthetase CYP11B2 knockout significantly increased urinary Na+ excretion in response to low-Na+ intake, decreased urinary K+ excretion but further increased plasma K+ concentrations in response to high-K+ intake, accompanied by attenuated urinary aldosterone excretion without affecting plasma aldosterone concentrations. Thus, we speculate that renal PRR may promote Na+ reabsorption and K+ excretion by stimulating renal CYP11B2-mediated aldosterone production. Therefore, in this project, we will use renal tubule-specific PRR and CYP11B2 knockout mice and collecting duct -specific renin knockout mice to clarify the important role of renal PRR-aldosterone signal in the regulation of Na+/K+ balance and blood pressure homeostasis, which will provide a new perspective and strategy for the clinical use of renin-angiotensin-aldosterone system inhibitors.