scholarly journals The Renin-Angiotensin System in the Development of Salt-Sensitive Hypertension in Animal Models and Humans

2010 ◽  
Vol 3 (4) ◽  
pp. 940-960 ◽  
Author(s):  
Beate Rassler
Keyword(s):  
Animal Models ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Salt Sensitive Hypertension

Salt-sensitive hypertension in chronic kidney disease: distal tubular mechanisms

2020 ◽  
Vol 319 (5) ◽  
pp. F729-F745
Author(s):  
Dominique M. Bovée ◽  
Catharina A. Cuevas ◽  
Robert Zietse ◽  
A. H. Jan Danser ◽  
Katrina M. Mirabito Colafella ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mineralocorticoid Receptor ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Distal Nephron ◽  
T Helper 17 ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Salt Sensitive Hypertension

Chronic kidney disease (CKD) causes salt-sensitive hypertension that is often resistant to treatment and contributes to the progression of kidney injury and cardiovascular disease. A better understanding of the mechanisms contributing to salt-sensitive hypertension in CKD is essential to improve these outcomes. This review critically explores these mechanisms by focusing on how CKD affects distal nephron Na+ reabsorption. CKD causes glomerulotubular imbalance with reduced proximal Na+ reabsorption and increased distal Na+ delivery and reabsorption. Aldosterone secretion further contributes to distal Na+ reabsorption in CKD and is not only mediated by renin and K+ but also by metabolic acidosis, endothelin-1, and vasopressin. CKD also activates the intrarenal renin-angiotensin system, generating intratubular angiotensin II to promote distal Na+ reabsorption. High dietary Na+ intake in CKD contributes to Na+ retention by aldosterone-independent activation of the mineralocorticoid receptor mediated through Rac1. High dietary Na+ also produces an inflammatory response mediated by T helper 17 cells and cytokines increasing distal Na+ transport. CKD is often accompanied by proteinuria, which contains plasmin capable of activating the epithelial Na+ channel. Thus, CKD causes both local and systemic changes that together promote distal nephron Na+ reabsorption and salt-sensitive hypertension. Future studies should address remaining knowledge gaps, including the relative contribution of each mechanism, the influence of sex, differences between stages and etiologies of CKD, and the clinical relevance of experimentally identified mechanisms. Several pathways offer opportunities for intervention, including with dietary Na+ reduction, distal diuretics, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and K+ or H+ binders.

scholarly journals Increased (pro)renin receptor expression in the subfornical organ of hypertensive humans

2018 ◽  
Vol 314 (4) ◽  
pp. H796-H804 ◽  
Author(s):  
Silvana G. Cooper ◽  
Darshan P. Trivedi ◽  
Rieko Yamamoto ◽  
Caleb J. Worker ◽  
Cheng-Yuan Feng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Animal Models ◽  
Systolic Blood Pressure ◽  
Renin Angiotensin System ◽  
Subfornical Organ ◽  
Antihypertensive Drug Therapy ◽  
Angiotensin System ◽  
Human Hypertension ◽  
Renin Angiotensin ◽  
The Brain

The central nervous system plays an important role in essential hypertension in humans and in animal models of hypertension through modulation of sympathetic activity and Na+ and body fluid homeostasis. Data from animal models of hypertension suggest that the renin-angiotensin system in the subfornical organ (SFO) of the brain is critical for hypertension development. We recently reported that the brain (pro)renin receptor (PRR) is a novel component of the brain renin-angiotensin system and could be a key initiator of the pathogenesis of hypertension. Here, we examined the expression level and cellular distribution of PRR in the SFO of postmortem human brains to assess its association with the pathogenesis of human hypertension. Postmortem SFO tissues were collected from hypertensive and normotensive human subjects. Immunolabeling for the PRR and a retrospective analysis of clinical data were performed. We found that human PRR was prominently expressed in most neurons and microglia, but not in astrocytes, in the SFO. Importantly, PRR levels in the SFO were elevated in hypertensive subjects. Moreover, PRR immunoreactivity was significantly correlated with systolic blood pressure but not body weight, age, or diastolic blood pressure. Interestingly, this correlation was independent of antihypertensive drug therapy. Our data indicate that PRR in the SFO may be a key molecular player in the pathogenesis of human hypertension and, as such, could be an important focus of efforts to understand the neurogenic origin of hypertension. NEW & NOTEWORTHY This study provides evidence that, in the subfornical organ of the human brain, the (pro)renin receptor is expressed in neurons and microglia cells but not in astrocytes. More importantly, (pro)renin receptor immunoreactivity in the subfornical organ is increased in hypertensive humans and is significantly correlated with systolic blood pressure.

Chronic Renin-Angiotensin System Activation Induced Neuroinflammation: Common Mechanisms Underlying Hypertension and Dementia?

2021 ◽  
pp. 1-13
Author(s):  
Shirley Tran ◽  
Sanjaya Kuruppu ◽  
Niwanthi W. Rajapakse
Keyword(s):  
Cognitive Impairment ◽  
Angiotensin Ii ◽  
Animal Models ◽  
Vascular Dementia ◽  
Transforming Growth Factor ◽  
Renin Angiotensin System ◽  
Current Evidence ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Chronic Activation

Hypertension is a major risk factor for the pathogenesis of vascular dementia and Alzheimer’s disease. Chronic activation of the renin-angiotensin system (RAS) contributes substantially to neuroinflammation. We propose that neuroinflammation arising from chronic RAS activation can initiate and potentiate the onset of hypertension and related dementia. Neuroinflammation induced by chronic activation of the RAS plays a key role in the pathogenesis of dementia. Increased levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and transforming growth factor (TGF)-β have been reported in brain tissue of vascular dementia patients and animal models of vascular dementia induced by either angiotensin II infusion or transverse aortic coarctation. It is proposed that neuronal cell death and synaptic dysfunction induced by neuroinflammation lead to cognitive impairment in dementia. The neuroprotective RAS pathway, regulated by angiotensin-converting enzyme 2 (ACE2) which converts angiotensin II into angiotensin-(1–7), can attenuate hypertension and dementia. Furthermore, the use of anti-hypertensive medications in preventing dementia or cognitive decline in hypertensive patients and animal models of dementia have mostly been beneficial. Current evidence suggests a strong link between RAS induced neuroinflammation and the onset of hypertension and dementia, which warrants further investigation. Strategies to counteract an overactive RAS and enhance the neuroprotective arm of the RAS may help prevent or improve cognitive impairment associated with hypertension.

scholarly journals Effects of omapatrilat on the renin-angiotensin system in salt-sensitive hypertension

2002 ◽  
Vol 15 (6) ◽  
pp. 557-564 ◽  
Author(s):  
C. M. Ferrario ◽  
R. D. Smith ◽  
B. Brosnihan ◽  
M. C. Chappell ◽  
V. M. Campese ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Salt Sensitive Hypertension
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