Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Curr Opin Nephrol Hypertens. 2012 Mar;21(2):171-8. doi: 10.1097/MNH.0b013e3283503068.
Despite decades of study, the pathogenesis of essential hypertension remains obscure, but the kidney appears to play a central role. Technology for manipulation of the mouse genome has been immensely valuable in dissecting pathways involved in blood pressure control. This review summarizes recent studies employing this technology to understand signaling pathways and specific cell lineages within the kidney that are involved in the regulation of sodium excretion impacting blood pressure homeostasis.
We review a series of recent studies of regulatory pathways affecting sodium excretion by the kidney including the renin-angiotensin system, the mineralocorticoid receptor, the endothelin system, nitric oxide, and the with-no-lysine (K)/sterile 20-like kinase pathway. We have specifically highlighted studies utilizing transgenic mouse models, which provide a powerful mechanism for defining the role of proteins and pathways on sodium balance and blood pressure in the intact organism.
These studies underscore the importance of the kidney in regulation of blood pressure and the pathogenesis of hypertension. Transgenic mouse models provide a powerful approach to identifying key cell lineages and molecular pathways causing hypertension. These pathways represent potential targets for novel antihypertensive therapies.
尽管已经进行了数十年的研究，但原发性高血压的发病机制仍不清楚，但肾脏似乎起着核心作用。操纵小鼠基因组的技术对于剖析参与血压控制的途径非常有价值。本综述总结了最近利用这项技术来理解涉及调节肾脏中钠排泄的信号通路和特定细胞谱系的研究，这些研究涉及调节影响血压稳态的钠排泄。
我们回顾了一系列关于影响肾脏钠排泄的调节途径的研究，包括肾素-血管紧张素系统、盐皮质激素受体、内皮素系统、一氧化氮和无赖氨酸（K）/无菌 20 样激酶途径。我们特别强调了利用转基因小鼠模型的研究，这些模型为在完整生物体中定义蛋白质和途径对钠平衡和血压的作用提供了一种强大的机制。
这些研究强调了肾脏在调节血压和高血压发病机制中的重要性。转基因小鼠模型为确定导致高血压的关键细胞谱系和分子途径提供了一种强大的方法。这些途径代表了新型抗高血压治疗的潜在靶点。
