scholarly journals Urinary soluble (pro)renin receptor excretion is associated with urine pH in humans

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254688
Author(s):  
Nobukazu Sasaki ◽  
Satoshi Morimoto ◽  
Chikahito Suda ◽  
Satoru Shimizu ◽  
Atsuhiro Ichihara
Keyword(s):  
Vitamin C ◽  
Ph Regulation ◽  
Collecting Duct ◽  
Renin Angiotensin System ◽  
Positive Association ◽  
Urine Ph ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Status ◽  
Soluble P

The (pro)renin receptor [(P)RR] binds to renin and its precursor prorenin to activate the tissue renin-angiotensin system. It is cleaved to generate soluble (P)RR and M8–9, a residual hydrophobic truncated protein. The (pro)renin receptor also functions as an intracellular accessory protein of vacuolar-type H+-ATPase, which plays an essential role in controlling the intracellular vesicular acid environment. Thus, in the kidney, (P)RR may play a role in transporting H+ to urine in the collecting duct. Although blood soluble (P)RR has been recognized as a biomarker reflecting the status of the tissue renin-angiotensin system and/or tissue (P)RR, the significance of urinary soluble (P)RR excretion has not been determined. Therefore, this study aimed to investigate the characteristics of urinary soluble (P)RR excretion. Urinary soluble (P)RR excretion was measured, and its association with background factors was investigated in 441 patients. Relationships between changes in urine pH due to vitamin C treatment, which reduce urine pH, and urinary soluble (P)RR excretion were investigated in 10 healthy volunteers. Urinary soluble (P)RR excretion was 1.46 (0.44–2.92) ng/gCre. Urine pH showed a significantly positive association with urinary soluble (P)RR excretion, independent of other factors. Changes in urine pH and urinary soluble (P)RR excretion due to vitamin C treatment were significantly and positively correlated (ρ = 0.8182, p = 0.0038). These data showed an association between urinary soluble (P)RR excretion and urine pH in humans, suggesting that (P)RR in the kidney might play a role in urine pH regulation.

scholarly journals The cortical collecting duct plays a pivotal role in kidney local renin-angiotensin system

2013 ◽  
Vol 154 (17) ◽  
pp. 643-649 ◽  
Author(s):  
Rózsa Csohány ◽  
Ágnes Prókai ◽  
Anna Kosik ◽  
J. Attila Szabó
Keyword(s):  
Animal Studies ◽  
Collecting Duct ◽  
Renin Angiotensin System ◽  
Juxtaglomerular Apparatus ◽  
Systemic Circulation ◽  
The Body ◽  
Signal Pathways ◽  
Cortical Collecting Duct ◽  
Angiotensin System ◽  
Renin Angiotensin

The renin-angiotensin system is one of the most important hormone systems in the body, and the regulations as well as the role in the juxtaglomerular apparatus are well known. The present review focuses on renin secretion in a recently described localization, the cortical collecting duct. The authors display it in parallel of the copying strategy of an adult and a developing kidney. Furthermore, based on different animal studies it highlights the local role of renin released from the collecting duct. In chronic angiotensin II-infused, 2-kidney, 1-clip hypertensive model as well as in diabetic rats the major source of (pro)renin is indeed the collecting duct. In this localization this hormone can reach both the systemic circulation and the interstitial renin-angiotensin system components including the newly described (pro)renin receptor, by which (pro)renin is able to locally activate pro-fibrotic intracellular signal pathways. Consequently, one can postulate that in the future renin may serve either as a new therapeutic target in nephropathy associated with both hypertension and diabetes or as an early diagnostic marker in chronic diseases leading to nephropathy. Orv. Hetil., 2013, 154, 643–649.

scholarly journals Interactions of Renin-Angiotensin System and COVID-19: The Importance of Daily Rhythms in ACE2, ADAM17 and TMPRSS2 Expression

2021 ◽  
pp. S177-S194
Author(s):  
J ZLACKÁ ◽  
K STEBELOVÁ ◽  
M ZEMAN ◽  
I HERICHOVÁ
Keyword(s):  
Renin Angiotensin System ◽  
Positive Association ◽  
Ang Ii ◽  
Virus Envelope ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Circadian Control ◽  
A Disintegrin And Metalloproteinase

Angiotensin-converting enzyme 2 (ACE2) was identified as a molecule that mediates the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several membrane molecules of the host cell must cooperate in this process. While ACE2 serves in a membrane receptor-mediating interaction with the surface spike (S) glycoprotein of SARS-CoV-2 located on the virus envelope, enzyme A disintegrin and metalloproteinase 17 (ADAM17) regulates ACE2 availability on the membrane and transmembrane protease serine 2 (TMPRSS2) facilitates virus-cell membrane fusion. Interestingly, ACE2, ADAM17 and TMPRSS2 show a daily rhythm of expression in at least some mammalian tissue. The circadian system can also modulate COVID-19 progression via circadian control of the immune system (direct, as well as melatonin-mediated) and blood coagulation. Virus/ACE2 interaction causes ACE2 internalization into the cell, which is associated with suppressed activity of ACE2. As a major role of ACE2 is to form vasodilatory angiotensin 1-7 from angiotensin II (Ang II), suppressed ACE2 levels in the lung can contribute to secondary COVID-19 complications caused by up-regulated, pro-inflammatory vasoconstrictor Ang II. This is supported by the positive association of hypertension and negative COVID-19 prognosis although this relationship is dependent on numerous comorbidities. Hypertension treatment with inhibitors of renin-angiotensin system does not negatively influence prognosis of COVID-19 patients. It seems that tissue susceptibility to SARS-CoV-2 shows negative correlation to ACE2 expression. However, in lungs of infected patient, a high ACE2 expression is associated with better outcome, compared to low ACE2 expression. Manipulation of soluble ACE2 levels is a promising COVID-19 therapeutic strategy.

scholarly journals Biochemical evaluation of the renin-angiotensin system: the good, bad, and absolute?

2016 ◽  
Vol 310 (2) ◽  
pp. H137-H152 ◽  
Author(s):  
Mark C. Chappell
Keyword(s):  
Renin Angiotensin System ◽  
Cellular Growth ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Angiotensin System ◽  
Physiological Regulation ◽  
Renin Angiotensin ◽  
Angiotensin Peptides ◽  
The Status ◽  
Biochemical Evaluation

The renin-angiotensin system (RAS) constitutes a key hormonal system in the physiological regulation of blood pressure through peripheral and central mechanisms. Indeed, dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies, and pharmacological blockade of this system by the inhibition of angiotensin-converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT1R) offers an effective therapeutic regimen. The RAS is now defined as a system composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS comprises the ACE-ANG II-AT1R axis that promotes vasoconstriction; water intake; sodium retention; and increased oxidative stress, fibrosis, cellular growth, and inflammation. In contrast, the nonclassical RAS composed primarily of the ANG II/ANG III-AT2R and the ACE2-ANG-(1–7)-AT7R pathways generally opposes the actions of a stimulated ANG II-AT1R axis. In lieu of the complex and multifunctional aspects of this system, as well as increased concerns on the reproducibility among laboratories, a critical assessment is provided on the current biochemical approaches to characterize and define the various components that ultimately reflect the status of the RAS.

scholarly journals ELABELA antagonizes intrarenal renin-angiotensin system to lower blood pressure and protects against renal injury

2020 ◽  
Vol 318 (5) ◽  
pp. F1122-F1135 ◽  
Author(s):  
Chuanming Xu ◽  
Fei Wang ◽  
Yanting Chen ◽  
Shiying Xie ◽  
Danielle Sng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Protein Expression ◽  
Collecting Duct ◽  
Protective Action ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Distal Nephron ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Intrarenal Ras

Emerging evidence has demonstrated that (pro)renin receptor (PRR)-mediated activation of intrarenal renin-angiotensin system (RAS) plays an essential role in renal handling of Na+ and water balance and blood pressure. The present study tested the possibility that the intrarenal RAS served as a molecular target for the protective action of ELABELA (ELA), a novel endogenous ligand of apelin receptor, in the distal nephron. By RNAscope and immunofluorescence, mRNA and protein expression of endogenous ELA was consistently localized to the collecting duct (CD). Apelin was also found in the medullary CDs as assessed by immunofluorescence. In cultured CD-derived M1 cells, exogenous ELA induced parallel decreases of full-length PRR (fPRR), soluble PRR (sPRR), and prorenin/renin protein expression as assessed by immunoblotting and medium sPRR and prorenin/renin levels by ELISA, all of which were reversed by 8-bromoadenosine 3′,5′-cyclic monophosphate. Conversely, deletion of PRR in the CD or nephron in mice elevated Apela and Apln mRNA levels as well as urinary ELA and apelin excretion, supporting the antagonistic relationship between the two systems. Administration of exogenous ELA-32 infusion (1.5 mg·kg−1·day−1, minipump) to high salt (HS)-loaded Dahl salt-sensitive (SS) rats significantly lowered mean arterial pressure, systolic blood pressure, diastolic blood pressure, and albuminuria, accompanied with a reduction of urinary sPRR, angiotensin II, and prorenin/renin excretion. HS upregulated renal medullary protein expression of fPRR, sPRR, prorenin, and renin in Dahl SS rats, all of which were significantly blunted by exogenous ELA-32 infusion. Additionally, HS-induced upregulation of inflammatory cytokines ( IL-1β, IL-2, IL-6, IL-17A, IFN-γ, VCAM-1, ICAM-1, and MCP-1), fibrosis markers ( TGF-β1, FN, Col1A1, PAI-1, and TIMP-1), and kidney injury markers ( NGAL, Kim-1, albuminuria, and urinary NGAL excretion) were markedly blocked by exogenous ELA infusion. Together, these results support the antagonistic interaction between ELA and intrarenal RAS in the distal nephron that appears to exert a major impact on blood pressure regulation.

scholarly journals MODULATION OF RENIN ANGIOTENSIN SYSTEM COMPONENTS BY HIGH GLUCOSE LEVELS IN CULTURE OF COLLECTING DUCT CELLS

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Ana Paula de Oliveira Leite ◽  
Danielle Aragão ◽  
Fernanda Aparecida Ronchi ◽  
Marie Nogueira ◽  
Lys Angela Mendes ◽  
...  
Keyword(s):  
High Glucose ◽  
Collecting Duct ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Glucose Levels ◽  
Duct Cells ◽  
System Components ◽  
Collecting Duct Cells

scholarly journals Succinate activates the collecting duct renin‐angiotensin system (RAS)

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Agnes Prokai ◽  
James Burford ◽  
Haykanush Gevorgyan ◽  
Zalan Peterfi ◽  
Sarah L Vargas ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Renin-Angiotensin System Induced Secondary Hypertension: The Alteration of Kidney Function and Structure

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Zahra Pezeshki ◽  
Mehdi Nematbakhsh
Keyword(s):  
Rat Model ◽  
Collecting Duct ◽  
Renin Angiotensin System ◽  
Inflammatory Cells ◽  
Secondary Hypertension ◽  
Ang Ii ◽  
Angiotensin System ◽  
Kidney Fibrosis ◽  
Renin Angiotensin ◽  
Hypertensive Rat

Long-term hypertension is known as a major risk factor for cardiovascular and chronic kidney disease (CKD). The Renin-angiotensin system (RAS) plays a key role in hypertension pathogenesis. Angiotensin II (Ang II) enhancement in Ang II-dependent hypertension leads to progressive CKD and kidney fibrosis. In the two-kidney one-clip model (2K1C), more renin is synthesized in the principal cells of the collecting duct than juxtaglomerular cells (JGCs). An increase of renal Ang I and Ang II levels and a decrease of renal cortical and medullary Ang 1–7 occur in both kidneys of the 2K1C hypertensive rat model. In addition, the activity of the angiotensin-converting enzyme (ACE) increases, while ACE2’s activity decreases in the medullary region of both kidneys in the 2K1C hypertensive model. Also, the renal prolyl carboxypeptidase (PrCP) expression and its activity reduce in the clipped kidneys. The imbalance in the production of renal ACE, ACE2, and PrCP expression causes the progression of renal injury. Intrarenal angiotensinogen (AGT) expression and urine AGT (uAGT) excretion rates in the unclipped kidney are greater than the clipped kidney in the 2K1C hypertensive rat model. The enhancement of Ang II in the clipped kidney is related to renin secretion, while the elevation of intrarenal Ang II in the unclipped kidney is related to stimulation of AGT mRNA and protein in proximal tubule cells by a direct effect of systemic Ang II level. Ang II-dependent hypertension enhances macrophages and T-cell infiltration into the kidney which increases cytokines, and AGT synthesis in proximal tubules is stimulated via cytokines. Accumulation of inflammatory cells in the kidney aggravates hypertension and renal damage. Moreover, Ang II-dependent hypertension alters renal Ang II type 1 & 2 receptors (AT1R & AT2R) and Mas receptor (MasR) expression, and the renal interstitial fluid bradykinin, nitric oxide, and cGMP response to AT1R, AT2R, or BK B2-receptor antagonists. Based on a variety of sources including PubMed, Google Scholar, Scopus, and Science-Direct, in the current review, we will discuss the role of RAS-induced secondary hypertension on the alteration of renal function.

Modulation of renin angiotensin system components by high glucose levels in the culture of collecting duct cells

2019 ◽  
Vol 234 (12) ◽  
pp. 22809-22818 ◽  
Author(s):  
A. P. O. Leite ◽  
Danielle S. Aragão ◽  
Marie D. Nogueira ◽  
Renata O. Pereira ◽  
Zaira P. Jara ◽  
...  
Keyword(s):  
High Glucose ◽  
Collecting Duct ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Glucose Levels ◽  
Duct Cells ◽  
System Components ◽  
Collecting Duct Cells
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