A Salt-Induced Reno-Cerebral Reflex Activates Renin-Angiotensin Systems and Promotes CKD Progression

Cao, Wei; Li, Aiqing; Wang, Liangliang; Zhou, Zicong; Su, Zhihua; Wei, Bin; Wilcox, Christopher S.; Hou, Fan Fan

doi:10.1681/asn.2014050518

Cited by 87 publications

(97 citation statements)

References 74 publications

(87 reference statements)

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“…; Cao et al . , ), but how they have their CNS effects is not yet clear. The neurohumoral changes that are triggered during the evolution of renal dysfunction, such as overactivity of the renin–angiotensin system (Cao et al .…”

Section: Role Of Brain Pericytes In Neurological Disorders Associatedmentioning

confidence: 99%

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The role of pericytes in brain disorders: from the periphery to the brain

Hirunpattarasilp

Attwell

Freitas

2019

Journal of Neurochemistry

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It is becoming increasingly apparent that disorders of the brain microvasculature contribute to many neurological disorders. In recent years it has become clear that a major player in these events is the capillary pericyte which, in the brain, is now known to control the blood–brain barrier, regulate blood flow, influence immune cell entry and be crucial for angiogenesis. In this review we consider the under‐explored possibility that peripheral diseases which affect the microvasculature, such as hypertension, kidney disease and diabetes, produce central nervous system (CNS) dysfunction by mechanisms affecting capillary pericytes within the CNS. We highlight how cellular messengers produced peripherally can act via signalling pathways within CNS pericytes to reshape blood vessels, restrict blood flow or compromise blood–brain barrier function, thus causing neuronal dysfunction. Increased understanding of how renin–angiotensin, Rho‐kinase and PDGFRβ signalling affect CNS pericytes may suggest novel therapeutic approaches to reducing the CNS effects of peripheral disorders.

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Section: Role Of Brain Pericytes In Neurological Disorders Associatedmentioning

confidence: 99%

“…The neurohumoral changes that are triggered during the evolution of renal dysfunction, such as overactivity of the renin–angiotensin system (Cao et al . , ) and its downstream pathways, including RhoA/ROCK pathway signalling (Lee et al . ; Loirand et al .…”

Section: Role Of Brain Pericytes In Neurological Disorders Associatedmentioning

confidence: 99%

The role of pericytes in brain disorders: from the periphery to the brain

Hirunpattarasilp

Attwell

Freitas

2019

Journal of Neurochemistry

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“…RAS genes are regulated by several factors, including hyperglycemia, high-salt, albumin overload, reduced availability of nitric oxide and increased uremic toxin [4,8,45,46]. Recent studies show that loss of Klotho, an antiaging protein, also leads to RAS activation in diseased kidneys [47].…”

Section: Regulation Of Ras Expressionmentioning

confidence: 99%

“…It is well recognized that intrarenal RAS activation is associated with the development and progression of chronic kidney disease (CKD) by blood pressure-dependent and –independent mechanisms [4–8]. RAS consists of several components including angiotensinogen (AGT), renin, angiotensin-converting enzyme (ACE) and the angiotensin II (Ang II) type 1 and type 2 receptors (AT1 and AT2).…”

Section: Introductionmentioning

confidence: 99%

Wnt/β-catenin signaling and renin–angiotensin system in chronic kidney disease

Zhou

Liu²

2016

Current Opinion in Nephrology and Hypertension

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Purpose of review Intrarenal activation of the renin–angiotensin system (RAS) plays an essential role in the pathogenesis of hypertension and chronic kidney diseases (CKD). However, how RAS genes are regulated in vivo was poorly understood until recently. This review focuses on recent findings of the transcriptional regulation of RAS components as well as their implication in developing novel strategies to treat the patients with CKD. Recent findings Bioinformatics analyses have uncovered the presence of putative binding sites for T cell factor (TCF)/β-catenin in the promoter region of all RAS genes. Both in vitro and in vivo studies confirm that Wnt/β-catenin is the master upstream regulator that controls the expression of all RAS components tested such as angiotensinogen, renin, angiotensin converting enzyme (ACE) and angiotensin II type I receptor (AT1) in the kidney. Targeted inhibition of Wnt/β-catenin, by either small molecule ICG-001 or endogenous Wnt antagonist Klotho, represses RAS activation and ameliorates proteinuria and kidney injury. Blockade of Wnt/β-catenin signaling also normalizes blood pressure in mouse model of CKD. Summary These recent studies identify Wnt/β-catenin as the master regulator that controls multiple RAS genes, and suggest that targeting this upstream signaling could be an effective strategy for the treatment of patients with hypertension and CKD.

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“…Dietary salt determines glomerulosclerosis and renal injury in rats with RRM (Cao et al . ), and to some extent, also in patients with CKD (Lipkowitz & Wilcox ). A high‐salt diet induces oxidative stress and impairs myogenic responses of afferent arterioles in mice with RRM (Lai et al .…”

mentioning

confidence: 99%

High‐salt diet induces outward remodelling of efferent arterioles in mice with reduced renal mass

et al. 2016

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Aim The glomerular filtration rate (GFR) falls progressively in chronic kidney disease (CKD) which is caused by a reduction in the number of functional nephrons. The dysfunctional nephron exhibits a lower glomerular capillary pressure that is induced by an unbalance between afferent and efferent arteriole. Therefore, we tested the hypothesis that oxidative stress induced by CKD differentially impairs the structure or function of efferent versus afferent arterioles. Methods C57BL/6 mice received sham operations (sham) or 5/6 nephrectomy (RRM) and 3 months of normal or high salt diet or tempol. GFR was assessed from the plasma inulin clearance, arteriolar remodeling from media/lumen area ratio, myogenic responses from changes in luminal diameter with increases in perfusion pressure and passive wall compliance from the wall stress/strain relationships. Results Mice with RRM fed a high salt (versus sham) had a lower GFR (553±25 versus 758±36μl/min/g kidney, p<0.01) and a larger efferent arteriolar diameter (9.6±0.8 versus 7.4±0.7μm, p<0.05) resulting in a lower media/lumen area ratio (1.4±0.1 versus 2.4±0.2, p<0.01). These alterations were corrected by tempol. The myogenic responses of efferent arterioles were about one-half that of afferent arterioles and were unaffected by RRM or salt. Passive wall compliance was reduced by high salt in both afferent and efferent arterioles. Conclusion A reduction in renal mass with a high salt diet induces oxidative stress that leads to an outward eutrophic remodeling in efferent arterioles and reduced wall compliance in both afferent and efferent arterioles. This may contribute to the lower GFR in this model of CKD.

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A Salt-Induced Reno-Cerebral Reflex Activates Renin-Angiotensin Systems and Promotes CKD Progression

Cited by 87 publications

References 74 publications

The role of pericytes in brain disorders: from the periphery to the brain

The role of pericytes in brain disorders: from the periphery to the brain

Wnt/β-catenin signaling and renin–angiotensin system in chronic kidney disease

High‐salt diet induces outward remodelling of efferent arterioles in mice with reduced renal mass

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