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

Xu, Quanbin; Jensen, Dane D.; Peng, Hua; Feng, Yi

doi:10.1016/j.pharmthera.2016.04.006

Cited by 52 publications

(55 citation statements)

References 109 publications

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Section: Discussionmentioning

confidence: 99%

“…The importance of the neuronal PRR in hypertension and other cardiovascular diseases has been demonstrated by a number of research groups (50,54). Despite extensive evidence supporting this involvement (54), the mechanisms of action of the PRR remain incompletely understood. We previously reported that PRR deletion in neurons or blockade of the PRR by an antagonist attenuates the development of DOCA salt-induced hypertension (1,34,35).…”

Section: Discussionmentioning

confidence: 99%

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Neuronal (pro)renin receptor regulates deoxycorticosterone-induced sodium intake

Trebak

Feng

2018

Physiological Genomics

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Increased sodium appetite is a physiological response to sodium deficiency; however, it has also been implicated in disease conditions such as congestive heart failure, kidney failure, and salt-sensitive hypertension. The central nervous system is the major regulator of sodium appetite and intake behavior; however, the neural mechanisms underlying this behavior remain incompletely understood. Here, we investigated the involvement of the (pro)renin receptor (PRR), a component of the brain renin-angiotensin system, in the regulation of sodium intake in a neuron-specific PRR knockout (PRRKO) mouse model generated previously in our laboratory. Sodium intake following deoxycorticosterone (DOCA) stimulation was tested by assessing the preference of mice for 0.9% saline or regular water in single-animal metabolic cages. Blood pressure was monitored in conscious, freely moving mice by a telemetry system. We found that saline intake and total fluid intake were significantly reduced in PRRKO mice following DOCA treatment compared with that in wild-type (WT) mice, whereas regular water intake was similar between the genotypes. Sodium preference and total sodium intake were significantly reduced in PRRKO mice compared with WT mice. PRRKO mice also excreted less urine and urinary sodium compared with WT mice following DOCA treatment, whereas potassium excretion was similar between the two groups. Finally, we found that the sodium balance, calculated by subtracting urinary sodium excretion from sodium intake, was greater in WT mice than in PRRKO mice. Collectively, these findings suggest that the neuronal PRR plays a regulatory role in DOCA-induced sodium intake.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neuronal (pro)renin receptor regulates deoxycorticosterone-induced sodium intake

Trebak

Feng

2018

Physiological Genomics

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“…Transgenic rats overexpressing human PRR ubiquitously are normotensive, but show progressive development of nephropathy (454), whereas transgenic rats with smooth muscle specific PRR overexpression are hypertensive at 6 mo of age, which could be due to intra-adrenal ANG II-induced aldosterone generation (103). Likewise, brain PRR is hypothesized to regulate ANG II-dependent hypertensive responses (576,1179). In addition, PRR-dependent, but AT 1 R-indepednent effects have been reported in neuronal cells, including ROS production (814) and iNOS mRNA induction (406).…”

Section: E (Pro)renin Receptormentioning

confidence: 99%

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

812

780

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The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (ATR) is believed to mediate most functions of ANG II in the system. ATR utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between ATR signaling pathways and other signaling pathways have been recognized. Accumulating evidence reveals the complexity of ANG II signal transduction in pathophysiology of the vasculature, heart, kidney, and brain, as well as several pathophysiological features, including inflammation, metabolic dysfunction, and aging. In this review, we provide a comprehensive update of the ANG II receptor signaling events and their functional significances for potential translation into therapeutic strategies. ATR remains central to the system in mediating physiological and pathophysiological functions of ANG II, and participation of specific signaling pathways becomes much clearer. There are still certain limitations and many controversies, and several noteworthy new concepts require further support. However, it is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.

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“…This dual function has led to the identification of PRR as a by guest on April 7, 2019 http://www.jbc.org/ Downloaded from potentially efficient therapeutic target. Specific PRR inhibition has been demonstrated to be beneficial in a range of diseases, including hypertension and diabetic nephropathy (9,10).…”

Section: Introductionmentioning

confidence: 99%

(Pro)renin receptor-mediated myocardial injury, apoptosis, and inflammatory response in rats with diabetic cardiomyopathy

Xia

Wang

et al. 2019

Journal of Biological Chemistry

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Excessive activation of the renin-angiotensin system (RAS) in diabetic cardiomyopathy (DCM) provokes a series of structural and functional abnormalities, and causes ventricular remodeling and heart failure in diabetes. (Pro)renin receptor (PRR) is a component of the RAS and has been reported to be up-regulated in some cardiovascular diseases. Furthermore, PRR blockade in some cardiovascular diseases, such as myocardial infarction and hypertension, has been demonstrated to reverse their pathogenesis. However, there have been few studies about the function of PRR in the pathogenesis of DCM. In this study, we hypothesized that PRR is involved in the pathogenesis of DCM and mediates myocardial injury in DCM. To explore the role of PRR in DCM, we evaluated the effects of PRR overexpression and knockdown on the DCM phenotype in vivo and in vitro. The results show that PRR overexpression exacerbates myocardial injury and the inflammatory response in rats with DCM. Conversely, PRR knockdown alleviates myocardial fibrosis, apoptosis, and the inflammatory response, reversing the cardiac dysfunction in rats with DCM. In cell experiments, PRR overexpression also up-regulated the protein expression of collagen I and fibronectin, aggravated the inflammatory response, and increased the production of reactive oxygen species (ROS), while PRR knockdown had the opposite effect.

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

Cited by 52 publications

References 109 publications

Neuronal (pro)renin receptor regulates deoxycorticosterone-induced sodium intake

Neuronal (pro)renin receptor regulates deoxycorticosterone-induced sodium intake

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

(Pro)renin receptor-mediated myocardial injury, apoptosis, and inflammatory response in rats with diabetic cardiomyopathy

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