| First Author | Peng H | Year | 2018 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 314 |
| Issue | 3 | Pages | H580-H592 |
| PubMed ID | 29350998 | Mgi Jnum | J:258923 |
| Mgi Id | MGI:6144152 | Doi | 10.1152/ajpheart.00310.2017 |
| Citation | Peng H, et al. (2018) Overexpression of the neuronal human (pro)renin receptor mediates angiotensin II-independent blood pressure regulation in the central nervous system. Am J Physiol Heart Circ Physiol 314(3):H580-H592 |
| abstractText | Despite advances in antihypertensive therapeutics, at least 15-20% of hypertensive patients have resistant hypertension through mechanisms that remain poorly understood. In this study, we provide a new mechanism for the regulation of blood pressure (BP) in the central nervous system (CNS) by the (pro)renin receptor (PRR), a recently identified component of the renin-angiotensin system that mediates ANG II formation in the CNS. Although PRR also mediates ANG II-independent signaling, the importance of these pathways in BP regulation is unknown. Here, we developed a unique transgenic mouse model overexpressing human PRR (hPRR) specifically in neurons (Syn-hPRR). Intracerebroventricular infusion of human prorenin caused increased BP in Syn-hPRR mice. This BP response was attenuated by a NADPH oxidase (NOX) inhibitor but not by antihypertensive agents that target the renin-angiotensin system. Using a brain-targeted genetic knockdown approach, we found that NOX4 was the key isoform responsible for the prorenin-induced elevation of BP in Syn-hPRR mice. Moreover, inhibition of ERK significantly attenuated the increase in NOX activity and BP induced by human prorenin. Collectively, our findings indicate that an ANG II-independent, PRR-mediated signaling pathway regulates BP in the CNS by a PRR-ERK-NOX4 mechanism. NEW & NOTEWORTHY This study characterizes a new transgenic mouse model with overexpression of the human (pro)renin receptor in neurons and demonstrated a novel angiotensin II-independent mechanism mediated by human prorenin and the (pro)renin receptor in the central regulation of blood pressure. |
