The critical role of the central nervous system (pro)renin receptor in regulating systemic blood pressure.
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.
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.
Quanbin
Q
Xu
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.
Dane D
DD
Jensen
Department of Pediatrics, Union Hospital, Tongji Medical College, Huangzhong University of Sciences and Technology, Wuhan, China.
Hua
H
Peng
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. Electronic address: yumeifeng@medicine.nevada.edu.
Yumei
Y
Feng
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012083:Renin / Q000378:metabolism / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000502:physiology; D000093342:Prorenin Receptor
D000959:Antihypertensive Agents; D009842:Oligopeptides; C000595796:PRO20 peptide; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D012083:Renin; D000093342:Prorenin Receptor
(Pro)renin receptor; (Pro)renin receptor antagonists; Antihypertensive drugs; Brain; Hypertension; Prorenin