The critical role of the central nervous system (pro)renin receptor in regulating systemic blood pressure

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• 作者：Quanbin Xu^a ; ^b ; Dane D. Jensen^a ; ^b ; Hua Peng^c ; Yumei Feng^a ; ^b ; ^{yumeifeng@medicine.nevada.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：RAS ; renin&ndash ; angiotensin system ; BP ; blood pressure ; PRR ; (pro)renin receptor ; AGT ; angiotensinogen ; Ang I ; angiotensin I ; Ang II ; angiotensin II ; ACE ; angiotensin-converting enzyme ; AT1R ; angiotensin II type 1 receptor ; AT2R ; angiotensin II type 2 receptor ; MAPKs ; mitogen-activated protein kinases ; ERK1/2 ; extracellular signal-regulated kinases 1 and 2 ; BBB ; blood&ndash ; brain barrier ; SFO ; subfornical organ ; AP ; area posterma ; PVN ; paraventricular nucleus of the hypothalamus ; RVLM ; rostral
• 刊名：Pharmacology and Therapeutics
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：164
• 期：Complete
• 页码：126-134
• 全文大小：1314 K

文摘

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.