Xu Quanbin, Jensen Dane D, Peng Hua, Feng Yumei
Department of Pharmacology, Center for Cardiovascular Research, University of Nevada School of Medicine, Reno, NV, USA; Department of Physiology & Cell Biology, Center for Cardiovascular Research, University of Nevada School of Medicine, Reno, NV, USA.
Department of Pediatrics, Union Hospital, Tongji Medical College, Huangzhong University of Sciences and Technology, Wuhan, China.
Pharmacol Ther. 2016 Aug;164:126-34. doi: 10.1016/j.pharmthera.2016.04.006. Epub 2016 Apr 23.
The systemic renin-angiotensin system (RAS) has long been recognized as a critically important system in blood pressure (BP) regulation. However, extensive evidence has shown that a majority of RAS components are also present in many tissues and play indispensable roles in BP regulation. Here, we review evidence that RAS components, notably including the newly identified (pro)renin receptor (PRR), are present in the brain and are essential for the central regulation of BP. Binding of the PRR to its ligand, prorenin or renin, increases BP and promotes progression of cardiovascular diseases in an angiotensin II-dependent and -independent manner, establishing the PRR a promising antihypertensive drug target. We also review the existing PRR blockers, including handle region peptide and PRO20, and propose a rationale for blocking prorenin/PRR activation as a therapeutic approach that does not affect the actions of the PRR in vacuolar H(+)-ATPase and development. Finally, we summarize categories of currently available antihypertensive drugs and consider future perspectives.
长期以来，全身肾素 - 血管紧张素系统（RAS）一直被认为是血压（BP）调节中至关重要的系统。然而，大量证据表明，大多数RAS组分也存在于许多组织中，并在血压调节中发挥不可或缺的作用。在此，我们综述了相关证据，即RAS组分，特别是新发现的（前）肾素受体（PRR），存在于大脑中，并且对于血压的中枢调节至关重要。PRR与其配体（即肾素原或肾素）结合，以血管紧张素II依赖和非依赖的方式升高血压并促进心血管疾病的进展，这使得PRR成为一个有前景的抗高血压药物靶点。我们还综述了现有的PRR阻滞剂，包括柄区肽和PRO20，并提出了阻断肾素原/PRR激活作为一种不影响PRR在液泡H(+) -ATP酶中的作用及发育的治疗方法的理论依据。最后，我们总结了目前可用的抗高血压药物类别并考虑了未来的前景。
