Epochs in the depressor/pressor balance of the renin–angiotensin system

2016 ◽  
Vol 130 (10) ◽  
pp. 761-771 ◽  
Author(s):  
Katrina M. Mirabito Colafella ◽  
Lucinda M. Hilliard ◽  
Kate M. Denton
Keyword(s):  
Extracellular Fluid ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Mas Receptor ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

The renin–angiotensin system (RAS) plays a commanding role in the regulation of extracellular fluid homoeostasis. Tigerstadt and Bergman first identified the RAS more than two centuries ago. By the 1980s a voyage of research and discovery into the mechanisms and actions of this system led to the development of drugs that block the RAS, which have become the mainstay for the treatment of cardiovascular and renal disease. In the last 25 years new components of the RAS have come to light, including the angiotensin type 2 receptor (AT2R) and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1–7) [Ang(1–7)]/Mas receptor (MasR) axis. These have been shown to counter the classical actions of angiotensin II (AngII) at the predominant angiotensin type 1 receptor (AT1R). Our studies, and those of others, have demonstrated that targeting these depressor RAS pathways may be therapeutically beneficial. It is apparent that the evolution of both the pressor and depressor RAS pathways is distinct throughout life and that the depressor/pressor balance of the RAS vary between the sexes. These temporal patterns of expression suggest that therapies targeting the RAS could be optimized for discrete epochs in life.

Local renin-angiotensin system regulates the differentiation of mesenchymal stem cells into insulin-producing cells through angiotensin type 2 receptor

Biochimie ◽  
2017 ◽  
Vol 137 ◽  
pp. 132-138 ◽  
Author(s):  
Nermin Abdel-hamid Sadik ◽  
Nadia Said Metwally ◽  
Olfat Gamil Shaker ◽  
Mahmoud Sanad Soliman ◽  
Ahmed Abdelaziz Mohamed ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Insulin Producing Cells ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

scholarly journals Covid-19: the renin–angiotensin system imbalance hypothesis

2020 ◽  
Vol 134 (11) ◽  
pp. 1259-1264 ◽  
Author(s):  
Katharina Lanza ◽  
Lucas G. Perez ◽  
Larissa B. Costa ◽  
Thiago M. Cordeiro ◽  
Vitria A. Palmeira ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Renin Angiotensin System ◽  
Disease Course ◽  
Ang Ii ◽  
Cellular Mechanisms ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Mas Receptor

Abstract The emergency of SARS-CoV-2 in China started a novel challenge to the scientific community. As the virus turns pandemic, scientists try to map the cellular mechanisms and pathways of SARS-CoV-2 related to the pathogenesis of Coronavirus Disease 2019 (Covid-19). After transmembrane angiotensin-converting enzyme 2 (ACE2) has been found to be SARS-CoV-2 receptor, we hypothesized an immune-hematological mechanism for Covid-19 based on renin–angiotensin system (RAS) imbalance to explain clinical, laboratory and imaging findings on disease course. We believe that exaggerated activation of ACE/Angiotensin II (Ang II)/Angiotensin Type 1 (AT1) receptor RAS axis in line with reduction of ACE2/Angiotensin-(1-7)/Mas receptor may exert a pivotal role in the pathogenesis of Covid-19. In this perspective, we discuss potential mechanisms and evidence on this hypothesis.

scholarly journals Sex-related differences in the intratubular renin-angiotensin system in two-kidney, one-clip hypertensive rats

2019 ◽  
Vol 317 (3) ◽  
pp. F670-F682 ◽  
Author(s):  
Sang Ho Lee ◽  
Yu Ho Lee ◽  
Su Woong Jung ◽  
Dong Jin Kim ◽  
Seon Hwa Park ◽  
...  
Keyword(s):  
Renal Artery ◽  
Renin Angiotensin System ◽  
Female Rats ◽  
Male Rats ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mas Receptor

The intratubular renin-angiotensin system (RAS) is thought to play an essential role in hypertensive renal disease, but information regarding sex-related differences in this system is limited. The present study investigated sex differences in the intratubular RAS in two-kidney, one-clip (2K1C) rats. A 2.5-mm clip was placed on the left renal artery of Sprague-Dawley rats, and rats were euthanized 3 or 5 wk after the operation. Systolic blood pressure increased in 2K1C rats in both sexes but was significantly higher in male rats than in female rats, and an antihypertensive effect was not observed in 2K1C ovariectomized (OVX) female rats. Compared with male 2K1C rats, intratubular angiotensin-converting enzyme (ACE) and ANG II were repressed, and intratubular ACE2, angiotensin (1–7), and Mas receptor were increased in both kidneys in female 2K1C rats 5 wk after surgery. Comparison with male and female rats and intratubular mRNA levels of ACE and ANG II type 1 receptor were augmented in OVX female rats, regardless of the clipping surgery 3 wk postoperation. ANG II type 2 receptor was upregulated in female rats with or without OVX; thus, the ANG II type 1-to-type 2 receptor ratio was higher in male rats than in female rats. In conclusion, female rats were protected from hypertensive renal and cardiac injury after renal artery clipping. An increase in the intratubular nonclassic RAS [ACE2/angiotensin (1–7)/Mas receptor] and a decrease in the ANG II type 1-to-type 2 receptor ratio could limit the adverse effects of the classic RAS during renovascular hypertension in female rats, and estrogen is suggested to play a primary role in the regulation of intratubular RAS components.

scholarly journals Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition

2010 ◽  
Vol 298 (1) ◽  
pp. F150-F157 ◽  
Author(s):  
Romer A. Gonzalez-Villalobos ◽  
Ryousuke Satou ◽  
Naro Ohashi ◽  
Laura C. Semprun-Prieto ◽  
Akemi Katsurada ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Ang Ii ◽  
Male Mice ◽  
Rt Pcr ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Induced Hypertension ◽  
Angiotensin Type

Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT1R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9–12 wk old) were distributed as controls ( n = 10), ANG II infused (ANG II = 8, 400 ng·kg−1·min−1 for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 ± 0.13, P < 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 ± 0.14, P < 0.05). ACE protein (by WB) was increased by ANG II (1.21 ± 0.08, P < 0.05), and it was reduced by ACEi alone (0.88 ± 0.07, P < 0.05) or in combination with ANG II (0.80 ± 0.07, P < 0.05). AT1R protein (by WB) was increased by ANG II (1.27 ± 0.06, P < 0.05) and ACEi (1.17 ± 0.06, P < 0.05) but not ANG II + ACEi [1.15 ± 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 ± 0.23, P < 0.05) and ACEi (1.57 ± 0.15, P < 0.05), but not ANG II + ACEi (1.10 ± 0.15, NS). No significant changes were observed in AGT, ACE, or AT1R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT1R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension.

scholarly journals The Identikit of Patient at Risk for Severe COVID-19 and Death: The Dysregulation of Renin-Angiotensin System as the Common Theme

2021 ◽  
Vol 10 (24) ◽  
pp. 5883
Author(s):  
Riccardo Sarzani ◽  
Massimiliano Allevi ◽  
Federico Giulietti ◽  
Chiara Di Pentima ◽  
Serena Re ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Adverse Outcomes ◽  
Virus Binding ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Increased Risk ◽  
Metabolic Conditions ◽  
Patient At Risk

Since the first months of the coronavirus disease 2019 (COVID-19) pandemic, several specific physiologic traits, such as male sex and older age, or health conditions, such as overweight/obesity, arterial hypertension, metabolic syndrome, and type 2 diabetes mellitus, have been found to be highly prevalent and associated with increased risk of adverse outcomes in hospitalized patients. All these cardiovascular morbidities are widespread in the population and often coexist, thus identifying a common patient phenotype, characterized by a hyper-activation of the “classic” renin-angiotensin system (RAS) and mediated by the binding of angiotensin II (Ang II) to the type 1-receptor. At the same time, the RAS imbalance was proved to be crucial in the genesis of lung injury after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, where angiotensin-converting-enzyme-2 (ACE2) is not only the receptor for SARS-CoV-2, but its down-regulation through internalization and shedding, caused by the virus binding, leads to a further dysregulation of RAS by reducing angiotensin 1-7 (Ang 1-7) production. This focused narrative review will discuss the main available evidence on the role played by cardiovascular and metabolic conditions in severe COVID-19, providing a possible pathophysiological link based on the disequilibrium between the two opposite arms of RAS.

scholarly journals Is angiotensin-(3–4) (Val-Tyr), the shortest angiotensin II-derived peptide, opening new vistas on the renin–angiotensin system?

2017 ◽  
Vol 18 (1) ◽  
pp. 147032031668933 ◽  
Author(s):  
Juliana Dias ◽  
Flavia Axelband ◽  
Lucienne S. Lara ◽  
Humberto Muzi-Filho ◽  
Adalberto Vieyra
Keyword(s):  
Renin Angiotensin System ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Ang Ii ◽  
Proximal Tubule Cells ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Kinase Pathway

Angiotensin-(3−4) (Ang-(3−4) or Val-Tyr) is the shorter angiotensin (Ang) II-derived peptide, formed through successive hydrolysis that culminates with the release of Val-Tyr as a dipeptide. It is formed both in plasma and in kidney from Ang II and Ang III, and can be considered a component of the systemic and organ-based renin–angiotensin system. It is potently antihypertensive in humans and rats, and its concerted actions on proximal tubule cells culminate in the inhibition of fluid reabsorption, hyperosmotic urinary excretion of Na+. At the renal cell signaling level, Ang-(3−4) counteracts Ang II-type 1 receptor-mediated responses by acting as an allosteric enhancer in Ang II-type 2 receptor populations that target adenosine triphosphate-dependent Ca2+ and Na+ transporters through a cyclic adenosine monophosphate-activated protein kinase pathway.

scholarly journals Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

2015 ◽  
Vol 308 (4) ◽  
pp. R238-R249 ◽  
Author(s):  
Jeffrey P. Coble ◽  
Justin L. Grobe ◽  
Alan Kim Johnson ◽  
Curt D. Sigmund
Keyword(s):  
Intracellular Signaling ◽  
Fluid Intake ◽  
Renin Angiotensin System ◽  
Subfornical Organ ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mitogen Activated Protein ◽  
Angiotensin Type

It is critical for cells to maintain a homeostatic balance of water and electrolytes because disturbances can disrupt cellular function, which can lead to profound effects on the physiology of an organism. Dehydration can be classified as either intra- or extracellular, and different mechanisms have developed to restore homeostasis in response to each. Whereas the renin-angiotensin system (RAS) is important for restoring homeostasis after dehydration, the pathways mediating the responses to intra- and extracellular dehydration may differ. Thirst responses mediated through the angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptors (AT2R) respond to extracellular dehydration and intracellular dehydration, respectively. Intracellular signaling factors, such as protein kinase C (PKC), reactive oxygen species (ROS), and the mitogen-activated protein (MAP) kinase pathway, mediate the effects of central angiotensin II (ANG II). Experimental evidence also demonstrates the importance of the subfornical organ (SFO) in mediating some of the fluid intake effects of central ANG II. The purpose of this review is to highlight the importance of the SFO in mediating fluid intake responses to dehydration and ANG II.

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