No Brain Renin–Angiotensin System

Diz, Debra I.; Chappell, Mark C.

doi:10.1161/hypertensionaha.117.09167

Cited by 30 publications

(20 citation statements)

References 28 publications

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“…However, low levels of renin were observed in many other studies ( Bader and Ganten, 2002 ; Lavoie et al, 2004 ) and, more importantly, the brain has high levels of prorenin and prorenin receptors, and prorenin bound to prorenin receptors provides catalytic properties similar to those of renin ( Nguyen and Contrepas, 2008 ; Valenzuela et al, 2010 ). This point has been discussed in detail by Sigmund et al, 2017 .…”

Section: The Brain Ras Dopamine and Rasmentioning

confidence: 84%

The intracellular renin-angiotensin system: Friend or foe. Some light from the dopaminergic neurons

Labandeira‐Garcia

Valenzuela

Costa-Besada

et al. 2021

Progress in Neurobiology

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Section: The Brain Ras Dopamine and Rasmentioning

confidence: 84%

The intracellular renin-angiotensin system: Friend or foe. Some light from the dopaminergic neurons

Labandeira‐Garcia

Valenzuela

Costa-Besada

et al. 2021

Progress in Neurobiology

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“…Indeed, a preponderance of evidence suggests the brain has the capacity for both. However, recent studies and editorial commentary highlight the surprisingly controversial nature of this conclusion (968,1086). Due to the complexity and vastness of this subject, we direct readers to other reviews that also cover the brain RAS (177,222,1156,1217).…”

Section: Ang II Signaling In the Brainmentioning

confidence: 99%

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

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

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821

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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“…However the role of ANG II in astrocytes rather than neurons still remains to be determined. On the other hand, it has recently been debated whether there is actually a brain RAS, letting alone an intracellular system [152–154]. Danser’s group argued that renin in the brain may represent plasma renin that is taken up and trapped in the brain, whereas ANG II in the brain may represent ANG II taken up from blood rather than locally synthesized [152,153].…”

Section: Intratubular Ras In the Kidney: Roles Of Intratubular And Inmentioning

confidence: 99%

“…Danser’s group argued that renin in the brain may represent plasma renin that is taken up and trapped in the brain, whereas ANG II in the brain may represent ANG II taken up from blood rather than locally synthesized [152,153]. But Sigmund’ group has argued that there is compelling evidence for the de novo production of all components of the RAS in the brain [154]. Clearly, the unresolved issue in the brain just as in the kidney is how much ANG II accumulates versus is synthesized locally.…”

Section: Intratubular Ras In the Kidney: Roles Of Intratubular And Inmentioning

confidence: 99%

Intratubular and intracellular renin–angiotensin system in the kidney: a unifying perspective in blood pressure control

Zhu

Zheng

et al. 2018

Clinical Science

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The renin-angiotensin system (RAS) is widely recognized as one of the most important vasoactive hormonal systems in the physiological regulation of blood pressure and the development of hypertension. This recognition is derived from, and supported by, extensive molecular, cellular, genetic, and pharmacological studies on the circulating (tissue-to-tissue), paracrine (cell-to-cell), and intracrine (intracellular, mitochondrial, nuclear) RAS during last several decades. Now, it is widely accepted that circulating and local RAS may act independently or interactively, to regulate sympathetic activity, systemic and renal hemodynamics, body salt and fluid balance, and blood pressure homeostasis. However, there remains continuous debate with respect to the specific sources of intratubular and intracellular RAS in the kidney and other tissues, the relative contributions of the circulating RAS to intratubular and intracellular RAS, and the roles of intratubular compared with intracellular RAS to the normal control of blood pressure or the development of angiotensin II (ANG II)-dependent hypertension. Based on a lecture given at the recent XI International Symposium on Vasoactive Peptides held in Horizonte, Brazil, this article reviews recent studies using mouse models with global, kidney- or proximal tubule-specific overexpression (knockin) or deletion (knockout) of components of the RAS or its receptors. Although much knowledge has been gained from cell- and tissue-specific transgenic or knockout models, a unifying and integrative approach is now required to better understand how the circulating and local intratubular/intracellular RAS act independently, or with other vasoactive systems, to regulate blood pressure, cardiovascular and kidney function.

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No Brain Renin–Angiotensin System

Cited by 30 publications

References 28 publications

The intracellular renin-angiotensin system: Friend or foe. Some light from the dopaminergic neurons

The intracellular renin-angiotensin system: Friend or foe. Some light from the dopaminergic neurons

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

Intratubular and intracellular renin–angiotensin system in the kidney: a unifying perspective in blood pressure control

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