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 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 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.

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.

Abstract 227: The Protective Effect of Kidney-Specific ACE Inhibition Against Chronic Angiotensin II Infusions is Associated with Blunted Intrarenal Renin-Angiotensin System Activation

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Jorge F Giani ◽  
Tea Djandjoulia ◽  
Nicholas Fetcher ◽  
Sebastien Fuchs ◽  
Dale M Seth ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Fold Increase ◽  
Ace Inhibition ◽  
Sham Operation ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Intrarenal Ras ◽  
Failed Induction

Introduction: The responses to chronic angiotensin (Ang) II infusions of gene-targeted mice lacking kidney angiotensin-converting enzyme (ACE), in terms of intrarenal Ang II accumulation, hypertension, sodium and water retention are all blunted or absent. The objective of this study was to determine if these reduced responses were associated with changes in the intrarenal renin-angiotensin system (RAS). METHODS: Mice lacking intrarenal ACE (ACE10/10) were generated by targeted homologous recombination placing the expression of ACE only in macrophages. As a result, these mice have normal circulating ACE levels, but no kidney ACE. Wild-type (WT) mice of the same background (C57Bl/J) served as controls. Mice were subjected to sham-operation or subcutaneous infusion of Ang II for two weeks (n=6-10, 400 ng/kg/min via osmotic minipump). Mean arterial pressure (MAP) was followed by telemetry. At the end of the experiment, the kidneys were collected for analysis. Ang II content was measured by RIA. Renal abundance of ACE, angiotensinogen (AGT) and Ang II receptor type 1 (AT1R) were determined by Western Blot in total kidney homogenates. Results: At baseline, the MAP of WT and ACE 10/10 mice was similar 110 ± 4 mmHg vs. 109 ± 3 mmHg respectively (p>0.05). However, when subjected to chronic Ang II infusions, the hypertensive response was blunted in ACE 10/10 mice (129 ± 6 mmHg) vs. WT (146 ± 5 mmHg; P<0.05). Also, intrarenal Ang II accumulation was lower in ACE10/10 mice (724 ± 81 fmol/g) vs. WT (1130 ± 105 fmol/g, p<0.05). In non-treated mice, intrarenal RAS components analysis revealed that the absence of ACE in ACE10/10 mice was accompanied by a significant reduction in AGT (0.41 ± 0.06) and increased AT1R expression (1.32 ± 0.05) when compared to WT (normalized to 1.00, p<0.05 in both instances). Importantly, after chronic Ang II infusions, AGT, ACE and AT1R expression increased in WT (1.36, 1.26 and 1.17 fold increase respectively compared to non-treated WT, p<0.05) but not in the ACE10/10 mice (1.19, 1.06, 0.89 fold increase respectively compared to non-treated ACE10/10, p>0.05). Conclusion: The blunted hypertension and Ang II accumulation of mice devoid of kidney ACE in response to Ang II infusions is associated with a failed induction of renal AGT and the AT1R.

The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment

2007 ◽  
Vol 292 (5) ◽  
pp. H2523-H2531 ◽  
Author(s):  
Steven J. Miller ◽  
Laura E. Norton ◽  
Michael P. Murphy ◽  
Michael C. Dalsing ◽  
Joseph L. Unthank
Keyword(s):  
Renin Angiotensin System ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Renin Angiotensin ◽  
Growth Impairment ◽  
Collateral Growth ◽  
Collateral Artery

Recent clinical and animal studies have shown that collateral artery growth is impaired in the presence of vascular risk factors, including hypertension. Available evidence suggests that angiotensin-converting enzyme inhibitors (ACEI) promote collateral growth in both hypertensive humans and animals; however, the specific mechanisms are not established. This study evaluated the hypothesis that collateral growth impairment in hypertension is mediated by excess superoxide produced by NAD(P)H oxidase in response to stimulation of the ANG II type 1 receptor. After ileal artery ligation, mesenteric collateral growth did not occur in untreated, young, spontaneously hypertensive rats. Significant luminal expansion occurred in collaterals of spontaneously hypertensive rats treated with the superoxide dismutase mimetic tempol, the NAD(P)H oxidase inhibitor apocynin, and the ACEI captopril, but not ANG II type 1 (losartan) or type 2 (PD-123319) receptor blockers. The ACEI enalapril produced equivalent reduction of arterial pressure as captopril but did not promote luminal expansion. This suggests the effects of captopril on collateral growth might result from its antioxidant properties. RT-PCR demonstrated that ANG II type 1 receptor and angiotensinogen expression was reduced in collaterals of untreated rats. This local suppression of the renin angiotensin system provides a potential explanation for the lack of effect of enalapril and losartan on collateral growth. The results demonstrate the capability of antioxidant therapies, including captopril, to reverse impaired collateral artery growth and the novel finding that components of the local renin angiotensin system are naturally suppressed in collaterals.

scholarly journals Alternative renin-angiotensin system pathways in adipose tissue and their role in the pathogenesis of obesity

2016 ◽  
Vol 50 (4) ◽  
pp. 229-240 ◽  
Author(s):  
M Slamkova ◽  
S Zorad ◽  
K Krskova
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Alternative Pathways ◽  
Metabolism Regulation ◽  
Mas Receptor ◽  
Glucose And Lipid Metabolism

AbstractAdipose tissue expresses all the renin-angiotensin system (RAS) components that play an important role in the adipogenesis, lipid and glucose metabolism regulation in an auto/paracrine manner. The classical RAS has been found to be over-activated during the adipose tissue enlargement, thus elevated generation of angiotensin II (Ang II) may contribute to the obesity pathogenesis. The contemporary view on the RAS has become more complex with the discovery of alternative pathways, including angiotensin-converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor, (pro)renin receptor, as well as angiotensin IV(Ang IV)/AT4 receptor. Ang-(1-7) via Mas receptor counteracts with most of the deleterious effects of the Ang II-mediated by AT1 receptor implying its beneficial role in the glucose and lipid metabolism, oxidative stress, inflammation, and insulin resistance. Pro(renin) receptor may play a role (at least partial) in the pathogenesis of the obesity by increasing the local production of Ang II in adipose tissue as well as triggering signal transduction independently of Ang II. In this review, modulation of alternative RAS pathways in adipose tissue during obesity is discussed and the involvement of Ang-(1-7), (pro)renin and AT4 receptors in the regulation of adipose tissue homeostasis and insulin resistance is summarized.

scholarly journals Nicotine and the renin-angiotensin system

2018 ◽  
Vol 315 (5) ◽  
pp. R895-R906 ◽  
Author(s):  
Joshua M. Oakes ◽  
Robert M. Fuchs ◽  
Jason D. Gardner ◽  
Eric Lazartigues ◽  
Xinping Yue
Keyword(s):  
Cigarette Smoking ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Regulatory Systems ◽  
Health And Disease ◽  
Former Smokers ◽  
New Generation

Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases (CVPD). Although cigarette smoking has been in constant decline since the 1950s, the introduction of e-cigarettes or electronic nicotine delivery systems 10 yr ago has attracted former smokers as well as a new generation of consumers. Nicotine is a highly addictive substance, and it is currently unclear whether e-cigarettes are “safer” than regular cigarettes or whether they have the potential to reverse the health benefits, notably on the cardiopulmonary system, acquired with the decline of tobacco smoking. Of great concern, nicotine inhalation devices are becoming popular among young adults and youths, emphasizing the need for awareness and further study of the potential cardiopulmonary risks of nicotine and associated products. This review focuses on the interaction between nicotine and the renin-angiotensin system (RAS), one of the most important regulatory systems on autonomic, cardiovascular, and pulmonary functions in both health and disease. The literature presented in this review strongly suggests that nicotine alters the homeostasis of the RAS by upregulating the detrimental angiotensin-converting enzyme (ACE)/angiotensin (ANG)-II/ANG II type 1 receptor axis and downregulating the compensatory ACE2/ANG-(1–7)/Mas receptor axis, contributing to the development of CVPD.

scholarly journals Role of neurons and glia in the CNS actions of the renin-angiotensin system in cardiovascular control

2015 ◽  
Vol 309 (5) ◽  
pp. R444-R458 ◽  
Author(s):  
Annette D. de Kloet ◽  
Meng Liu ◽  
Vermalí Rodríguez ◽  
Eric G. Krause ◽  
Colin Sumners
Keyword(s):  
Blood Pressure ◽  
Glial Cell ◽  
Renin Angiotensin System ◽  
Cardiovascular Control ◽  
Health Concern ◽  
Ang Ii ◽  
Ongoing Research ◽  
Angiotensin System ◽  
Renin Angiotensin

Despite tremendous research efforts, hypertension remains an epidemic health concern, leading often to the development of cardiovascular disease. It is well established that in many instances, the brain plays an important role in the onset and progression of hypertension via activation of the sympathetic nervous system. Further, the activity of the renin-angiotensin system (RAS) and of glial cell-mediated proinflammatory processes have independently been linked to this neural control and are, as a consequence, both attractive targets for the development of antihypertensive therapeutics. Although it is clear that the predominant effector peptide of the RAS, ANG II, activates its type-1 receptor on neurons to mediate some of its hypertensive actions, additional nuances of this brain RAS control of blood pressure are constantly being uncovered. One of these complexities is that the RAS is now thought to impact cardiovascular control, in part, via facilitating a glial cell-dependent proinflammatory milieu within cardiovascular control centers. Another complexity is that the newly characterized antihypertensive limbs of the RAS are now recognized to, in many cases, antagonize the prohypertensive ANG II type 1 receptor (AT1R)-mediated effects. That being said, the mechanism by which the RAS, glia, and neurons interact to regulate blood pressure is an active area of ongoing research. Here, we review the current understanding of these interactions and present a hypothetical model of how these exchanges may ultimately regulate cardiovascular function.

scholarly journals The vascular renin-angiotensin system contributes to blunted vasodilation induced by transient high pressure in human adipose microvessels

2014 ◽  
Vol 307 (1) ◽  
pp. H25-H32 ◽  
Author(s):  
Matthew J. Durand ◽  
Shane A. Phillips ◽  
Michael E. Widlansky ◽  
Mary F. Otterson ◽  
David D. Gutterman
Keyword(s):  
Polyethylene Glycol ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Intraluminal Pressure ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Pressure Sensitive ◽  
Endothelial Denudation

Increased intraluminal pressure can reduce endothelial function in resistance arterioles; however, the mechanism of this impairment is unknown. The purpose of this study was to determine the effect of local renin-angiotensin system inhibition on the pressure-induced blunting of endothelium-dependent vasodilation in human adipose arterioles. Arterioles (100–200 μm) were dissected from fresh adipose surgical specimens, cannulated onto glass micropipettes, pressurized to an intraluminal pressure of 60 mmHg, and constricted with endothelin-1. Vasodilation to ACh was assessed at 60 mmHg and again after a 30-min exposure to an intraluminal pressure of 150 mmHg. The vasodilator response to ACh was significantly reduced in vessels exposed to 150 mmHg. Exposure of the vessels to the superoxide scavenger polyethylene glycol-SOD (100 U/ml), the ANG II type 1 receptor antagonist losartan (10−6 mol/l), or the angiotensin-converting enzyme inhibitor captopril (10−5 mol/l) prevented the pressure-induced reduction in ACh-dependent vasodilation observed in untreated vessels. High intraluminal pressure had no effect on papaverine-induced vasodilation or ANG II sensitivity. Increased intraluminal pressure increased dihydroethidium fluorescence in cannulated vessels, which could be prevented by polyethylene glycol-SOD or losartan treatment and endothelial denudation. These data indicate that high intraluminal pressure can increase vascular superoxide and reduce nitric oxide-mediated vasodilation via activation of the vascular renin-angiotensin system. This study provides evidence showing that the local renin-angiotensin system in the human microvasculature may be pressure sensitive and contribute to endothelial dysfunction after acute bouts of hypertension.

Improvement of insulin sensitivity by antagonism of the renin-angiotensin system

2007 ◽  
Vol 293 (3) ◽  
pp. R974-R980 ◽  
Author(s):  
Erik J. Henriksen
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Transport ◽  
Renin Angiotensin System ◽  
Whole Body ◽  
Ang Ii ◽  
Angiotensin System ◽  
Skeletal Muscle Insulin Resistance

The reduced capacity of insulin to stimulate glucose transport into skeletal muscle, termed insulin resistance, is a primary defect leading to the development of prediabetes and overt type 2 diabetes. Although the etiology of this skeletal muscle insulin resistance is multifactorial, there is accumulating evidence that one contributor is overactivity of the renin-angiotensin system (RAS). Angiotensin II (ANG II) produced from this system can act on ANG II type 1 receptors both in the vascular endothelium and in myocytes, with an enhancement of the intracellular production of reactive oxygen species (ROS). Evidence from animal model and cultured skeletal muscle cell line studies indicates ANG II can induce insulin resistance. Chronic ANG II infusion into an insulin-sensitive rat produces a markedly insulin-resistant state that is associated with a negative impact of ROS on the skeletal muscle glucose transport system. ANG II treatment of L6 myocytes causes impaired insulin receptor substrate (IRS)-1-dependent insulin signaling that is accompanied by augmentation of NADPH oxidase-mediated ROS production. Further critical evidence has been obtained from the TG(mREN2)27 rat, a model of RAS overactivity and insulin resistance. The TG(mREN2)27 rat displays whole body and skeletal muscle insulin resistance that is associated with local oxidative stress and a significant reduction in the functionality of the insulin receptor (IR)/IRS-1-dependent insulin signaling. Treatment with a selective ANG II type 1 receptor antagonist leads to improvements in whole body insulin sensitivity, enhanced insulin-stimulated glucose transport in muscle, and reduced local oxidative stress. In addition, exercise training of TG(mREN2)27 rats enhances whole body and skeletal muscle insulin action. However, these metabolic improvements elicited by antagonism of ANG II action or exercise training are independent of upregulation of IR/IRS-1-dependent signaling. Collectively, these findings support targeting the RAS in the design of interventions to improve metabolic and cardiovascular function in conditions of insulin resistance associated with prediabetes and type 2 diabetes.

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