Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
Curr Opin Nephrol Hypertens. 2018 Jan;27(1):1-7. doi: 10.1097/MNH.0000000000000373.
The renin-angiotensin system (RAS) plays a critical role in the pathogenesis of hypertension. Homeostatic actions of the RAS, such as increasing blood pressure (BP) and vasoconstriction, are mediated via type 1 (AT1) receptors for angiotensin II. All components of the RAS are present in the renal proximal tubule, which reabsorbs the bulk of the glomerular filtrate, making this segment of the nephron a location of great interest for solute handling under RAS influence. This review highlights recent studies that illustrate the key role of renal proximal tubule AT1 receptors in BP regulation.
A variety of investigative approaches have demonstrated that angiotensin II signaling via AT1a receptors, specifically in the renal proximal tubule, is a major regulator of BP and sodium homeostasis. Reduction of proximal tubule AT1a receptors led to lower BPs, whereas overexpression generally caused increased BPs.
AT1a receptors in the proximal tubule are critical to the regulation of BP by the kidney and the RAS. The pattern of BP modulation is associated with alterations in sodium transporters. As a key site for sodium homeostasis, the renal proximal tubule could hence be a potential target in the treatment of hypertension.
目的综述：肾素-血管紧张素系统（RAS）在高血压发病机制中起着关键作用。RAS 的稳态作用，如增加血压（BP）和血管收缩，是通过血管紧张素 II 的 1 型（AT1）受体介导的。RAS 的所有成分都存在于肾脏近端小管中，近端小管重吸收大部分肾小球滤过液，使这一段肾单位成为受 RAS 影响下溶质处理的重要部位。这篇综述强调了最近的研究，这些研究说明了肾脏近端小管 AT1 受体在血压调节中的关键作用。
最新发现：各种研究方法表明，通过 AT1a 受体的血管紧张素 II 信号转导，特别是在肾脏近端小管中，是血压和钠稳态的主要调节因子。近端小管 AT1a 受体的减少导致血压降低，而过度表达通常导致血压升高。
总结：近端小管中的 AT1a 受体对肾脏和 RAS 调节血压至关重要。血压调节模式与钠转运体的改变有关。由于近端小管是钠稳态的关键部位，因此它可能成为高血压治疗的潜在靶点。
