HORMONAL REGULATION OF BLOOD PRESSURE

肾细胞色素P450系统与花生四烯酸(AA)的关系 新陈代谢和血压控制已成为核心内容，并已 为PPG更新提供了主题统一。头五年给了我 细胞色素压倒一切的重要性的令人信服的证据 P450依赖的氨基酸(P450-AA)代谢物的未来发展方向 PPG。我们开发了一种方法来改变AA Metabo的肾脏生产- LITS通过干扰P450系统，鉴定出新的P450-AA 能通过影响血管运动影响血压的代谢物 和离子运动。 1)延髓粗大的Henle‘s环升支的运输功能 (MTALH)和血管张力的调节。2)糖皮质激素引起的改变 他们的肾内活动。3)肾血管扩张剂机制。4)有丝分裂 和信号转导。5)青年自发性高血压大鼠高血压的发生。 上述项目使用了各种技术和方法 不同的学科，以实现综合和全面的方法 总体假设：肾细胞色素P450依赖的AA代谢物 参与与肾脏相关的血管和转运机制 血压的调节与高血压的病理生理学。 这些项目严重依赖于GC-MS核心设施 组织和细胞产生的P450-AA代谢物的结构分析 在肾脏内。此外，需要一个细胞培养核心来满足 所有项目的需求，以解决P450-AA的细胞生物学 代谢物，包括对第二信使、管状转运的影响 P450-AA代谢产物的作用机制及跨细胞代谢。

The renal cytochrome P450 system as it relates to arachidonic acid (AA) metabolism and blood pressure control has become the centerpiece and has provided thematic unity for the PPG renewal. The first five years gave convincing testimony to the overriding importance of cytochrome P450-dependent-AA (P450-AA) metabolites to the future directions of the PPG. We developed the means to modify the renal production of AA metabo- lites by perturbing the P450 system, and identified novel P450-AA metabolites capable of affecting blood pressure by influencing vasomotion and ion movement. 1)Transport function of the medullary thick ascending limb of Henle's loop (mTALH), and regulation of vascular tone. 2)Glucocorticoid-induced changes in their intrarenal activity. 3)Renal vasodilator mechanisms. 4)Mitogenesis and signal transduction. 5)Development of hypertension in the young SHR. The above Projects make use of a variety of techniques and methods from diverse disciplines to arrive at an integrated and comprehensive approach to the Overall Hypothesis: Renal cytochrome P450-dependent-AA metabolites participate in renal vascular and transport mechanisms relevant to the regulation of blood pressure and to the pathophysiology of hypertension. These Projects are heavily dependent upon a GC-MS Core Facility for structural analysis of P450-AA metabolites generated by tissues and cells within the kidney. In addition, a Cell Culture Core is required to meet the needs of all Projects in order to address the cell biology of P450-AA metabolites, including effects on second messengers, tubular transport mechanisms and transcellular metabolism of P450-AA metabolites.