Le Thu H, Coffman Thomas M
Division of Nephrology and Department of Medicine, Duke University and Durham VA Medical Centers, Durham, North Carolina 27710, USA.
Curr Opin Nephrol Hypertens. 2008 Jan;17(1):57-63. doi: 10.1097/MNH.0b013e3282f2fd39.
The renin-angiotensin system plays a key role in the regulation of blood pressure and fluid homeostasis. Owing to its critical contribution to blood pressure control, abnormalities of any component in this system can lead to hypertension and cardiovascular diseases. In this review, we will highlight studies using this approach to uncover new perspectives on the physiology of the renin-angiotensin system.
Over the past decade, application of techniques for manipulating the genome of living animals, including gene targeting through homologous recombination in embryonic stem cells, has provided unique insights into the complex biology of the renin-angiotensin system. Along with advances in understanding functions of the classical components of the system, gene targeting has clarified the functions of newly discovered angiotensin-converting enzyme homologues.
Since pharmacological antagonists of the renin-angiotensin system are widely used in clinical medicine, advances in the gene-targeting experiments of the system have helped to clarify the mechanisms of action of these agents and may provide clues for improved approaches for the treatment of hypertension and kidney diseases.
肾素-血管紧张素系统在血压调节和体液平衡中起关键作用。由于其对血压控制的重要贡献，该系统中任何成分的异常都可导致高血压和心血管疾病。在本综述中，我们将重点介绍利用这种方法揭示肾素-血管紧张素系统生理学新观点的研究。
在过去十年中，包括通过胚胎干细胞同源重组进行基因靶向在内的操纵活体动物基因组技术的应用，为肾素-血管紧张素系统复杂生物学提供了独特见解。随着对该系统经典成分功能理解的进展，基因靶向已阐明新发现的血管紧张素转换酶同源物的功能。
由于肾素-血管紧张素系统的药理拮抗剂在临床医学中广泛使用，该系统基因靶向实验的进展有助于阐明这些药物的作用机制，并可能为改善高血压和肾脏疾病的治疗方法提供线索。
