scholarly journals Involvement of the Intrarenal Renin-Angiotensin System in Experimental Models of Glomerulonephritis

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Maki Urushihara ◽  
Yukiko Kinoshita ◽  
Shuji Kondo ◽  
Shoji Kagami
Keyword(s):  
Blood Pressure ◽  
Intracellular Signaling ◽  
Renin Angiotensin System ◽  
Experimental Models ◽  
At1 Receptor ◽  
Biologically Active ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Proinflammatory Mediators

The intrarenal renin-angiotensin system (RAS) has several pathophysiologic functions not only in blood pressure regulation but also in the development of glomerulonephritis (GN). Angiotensin II (Ang II) is the biologically active product of the RAS. Locally produced Ang II induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation, regulates the gene expression of bioactive substances, and activates multiple intracellular signaling pathways, leading to tissue damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, cell proliferation, and extracellular matrix synthesis, which facilitates glomerular injury. Previous studies have shown that angiotensin-converting enzyme inhibitors and/or AT1 receptor blockers have beneficial effects in experimental GN models and humans with various types of GN, and that these effects are more significant than their suppressive effects on blood pressure. In this paper, we focus on intrarenal RAS activation in the pathophysiology of experimental models of GN.

Abolition of long-term vascular influence of renin-angiotensin system

1990 ◽  
Vol 259 (2) ◽  
pp. H543-H553
Author(s):  
R. D. Randall ◽  
B. G. Zimmerman
Keyword(s):  
Blood Pressure ◽  
Vascular Tissue ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Ang Ii ◽  
Flow Measurements ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Normal Controls

Rabbits were bilaterally nephrectomized for 24 h or received an angiotensin-converting enzyme (ACE) inhibitor chronically (5 days) before an acute experiment. Conductance responses to sympathetic nerve stimulation (SNS) (0.25, 0.75, and 2.25 Hz) and norepinephrine (NE) administration (0.2, 0.6, and 1.8 micrograms ia) were determined from simultaneous blood pressure and iliac blood flow measurements. Conductance responses to SNS were significantly reduced in nephrectomized (44, 26, and 20%) and chronic ACE inhibition (39, 31, and 24%) groups compared with normal controls, whereas conductance responses to NE were unchanged. Continuous infusion of angiotensin II (ANG II) for 24 h restored the depressed responses to SNS in nephrectomized and chronic ACE inhibition groups compared with normal controls but did not change conductance responses to NE. Acute ACE inhibition did not affect the conductance responses to SNS or NE compared with controls. Vascular tissue ACE activity was inhibited to a similar degree (50%) in both acute and chronic ACE inhibition groups compared with normal rabbits. Sodium depletion increased the conductance responses to SNS (30 and 24% at 0.25 and 0.75 Hz, respectively), but responses to NE were not affected. Chronic ACE inhibition significantly attenuated the conductance responses to SNS and slightly decreased responses to NE in sodium-depleted rabbits. Thus, in the anesthetized rabbit, the renin-angiotensin system potentiates the effect of SNS, presumably by ANG II acting at a prejunctional site, and this effect of ANG II appears to be long term in nature. Therefore, the renin-angiotensin system exerts a physiological role in the control of blood pressure in addition to the ability of this system to support arterial pressure in pathophysiological states.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19, and the Renin-Angiotensin System

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1350-1367 ◽  
Author(s):  
Matthew A. Sparks ◽  
Andrew M. South ◽  
Andrew D. Badley ◽  
Carissa M. Baker-Smith ◽  
Daniel Batlle ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Experimental Models ◽  
Multiple Organ ◽  
Host Cells ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Organ Systems

The coronavirus disease 2019 (COVID-19) pandemic is associated with significant morbidity and mortality throughout the world, predominantly due to lung and cardiovascular injury. The virus responsible for COVID-19—severe acute respiratory syndrome coronavirus 2—gains entry into host cells via ACE2 (angiotensin-converting enzyme 2). ACE2 is a primary enzyme within the key counter-regulatory pathway of the renin-angiotensin system (RAS), which acts to oppose the actions of Ang (angiotensin) II by generating Ang-(1–7) to reduce inflammation and fibrosis and mitigate end organ damage. As COVID-19 spans multiple organ systems linked to the cardiovascular system, it is imperative to understand clearly how severe acute respiratory syndrome coronavirus 2 may affect the multifaceted RAS. In addition, recognition of the role of ACE2 and the RAS in COVID-19 has renewed interest in its role in the pathophysiology of cardiovascular disease in general. We provide researchers with a framework of best practices in basic and clinical research to interrogate the RAS using appropriate methodology, especially those who are relatively new to the field. This is crucial, as there are many limitations inherent in investigating the RAS in experimental models and in humans. We discuss sound methodological approaches to quantifying enzyme content and activity (ACE, ACE2), peptides (Ang II, Ang-[1–7]), and receptors (types 1 and 2 Ang II receptors, Mas receptor). Our goal is to ensure appropriate research methodology for investigations of the RAS in patients with severe acute respiratory syndrome coronavirus 2 and COVID-19 to ensure optimal rigor and reproducibility and appropriate interpretation of results from these investigations.

Modification of the pulmonary renin–angiotensin system and lung structural remodelling in congestive heart failure

2006 ◽  
Vol 111 (3) ◽  
pp. 217-224 ◽  
Author(s):  
Frederic Lefebvre ◽  
Annick Préfontaine ◽  
Angelino Calderone ◽  
Alexandre Caron ◽  
Jean-François Jasmin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Coronary Artery Ligation ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Lung Remodelling

Lung structural remodelling, characterized by myofibroblast proliferation and collagen deposition, contributes to impaired functional capacity in CHF (congestive heart failure). As the lung is the primary site for the formation of Ang II (angiotensin II), local modifications of this system could contribute to lung remodelling. Rats with CHF, induced following myocardial infarction (MI) via coronary artery ligation, were compared with sham-operated controls. The MI group developed lung remodelling as confirmed by morphometric measurements and immunohistochemistry. Pulmonary Ang II concentrations increased more than 6-fold (P<0.01), and AT1 (Ang II type 1) receptor expression was elevated by 3-fold (P<0.01) with evidence of distribution in myofibroblasts. AT2 (Ang II type 2) receptor expression was unchanged. In isolated lung myofibroblasts, AT1 and AT2 receptors were expressed, and Ang II stimulated proliferation as measured by [3H]thymidine incorporation. In normal rats, chronic intravenous infusion of Ang II (0.5 mg·kg−1 of body weight·day−1) for 28 days significantly increased mean arterial pressure (P<0.05), without pulmonary hypertension, lung remodelling or a change in AT1 receptor expression. We conclude that there is a modification of the pulmonary renin–angiotensin system in CHF, with increased Ang II levels and AT1 receptor expression on myofibroblasts. Although this may contribute to lung remodelling, the lack of effect of increased plasma Ang II levels alone suggests the importance of local pulmonary Ang II levels combined with the effect of other factors activated in CHF.

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.

Differential effect of tetradecythioacetic acid on the renin-angiotensin system and blood pressure in SHR and 2-kidney, 1-clip hypertension

2007 ◽  
Vol 293 (3) ◽  
pp. F839-F845 ◽  
Author(s):  
Liliana Monica Bivol ◽  
Rolf Kristian Berge ◽  
Bjarne Magnus Iversen
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Reduction ◽  
Kidney Tissue ◽  
Renin Angiotensin System ◽  
Minor Effect ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Blood Pressure Lowering Effect ◽  
Angiotensin System ◽  
Renin Angiotensin

The tetradecythioacetic acid (TTA) is a modified fatty acid known to exhibit pleiotropic effects. First, we compared the effect of TTA on the blood pressure in spontaneously hypertensive rats (SHR) with two-kidney, one-clip (2K1C)-hypertensive rats. Second, we examined mechanisms involved in the blood pressure reduction. TTA had minor effect on systolic blood pressure (SBP) in young SHR up to 8 wk of age. In 2K1C we confirmed the blood pressure-lowering effect of TTA (SBP: 173 ± 4 before vs. 138 ± 3 mmHg after TTA, P < 0.001). No effect on SBP was seen in Wistar-Kyoto rat (WKY) controls. Plasma renin activity (PRA) was low in SHR and WKY controls and TTA did not change it. PRA decreased from 22.9 ± 1.3 to 16.2 ± 2.2 ng·ml−1·h−1 ( P = 0.02) in 2K1C. Plasma ANG II concentration declined from 101 ± 3 to 81 ± 5 fmol/l after TTA treatment ( P = 0.005). In the clipped kidney, tissue ANG I concentration decreased from 933 ± 68 to 518 ± 60 fmol/g tissue ( P = 0.001), and ANG II decreased from 527 ± 38 to 149 ± 21 fmol/g tissue ( P < 0.001) after TTA treatment. In the nonclipped kidney, TTA did not change ANG I and moderately reduced ANG II levels. The renal blood flow response to injection of ANG II into the nonclipped kidney was blunted compared with controls and normalized with TTA treatment (10 ± 2 before vs. 20 ± 2%, P < 0.001). The results indicate that TTA downregulates the renin-angiotensin system in high renin animals but has no effect in low renin models.

scholarly journals Kallikrein–kinin system as the dominant mechanism to counteract hyperactive renin–angiotensin system

2017 ◽  
Vol 95 (10) ◽  
pp. 1117-1124 ◽  
Author(s):  
Domenico Regoli ◽  
Fernand Gobeil
Keyword(s):  
Renin Angiotensin System ◽  
Biologically Active ◽  
Ang Ii ◽  
Kinin System ◽  
Angiotensin System ◽  
Dominant Mechanism ◽  
Renin Angiotensin ◽  
First Choice ◽  
Kallikrein Kinin System ◽  
The Impact

The renin–angiotensin system (RAS) generates, maintains, and makes worse hypertension and cardiovascular diseases (CVDs) through its biologically active component angiotensin II (Ang II), that causes vasoconstriction, sodium retention, and structural alterations of the heart and the arteries. A few endogenous vasodilators, kinins, natriuretic peptides, and possibly angiotensin (1-7), exert opposite actions and may provide useful therapeutic agents. As endothelial autacoids, the kinins are potent vasodilators, active natriuretics, and protectors of the endothelium. Indeed, the kallikrein–kinin system (KKS) is considered the dominant mechanism for counteracting the detrimental effects of the hyperactive RAS. The 2 systems, RAS and KKS, are controlled by the angiotensin-converting enzyme (ACE) that generates Ang II and inactivates the kinins. Inhibitors of ACE can reduce the impact of Ang II and potentiate the kinins, thus contributing to restore the cardiovascular homeostasis. In the last 20 years, ACE-inhibitors (ACE-Is) have become the drugs of first choice for the treatments of the major CVDs. ACE-Is not only reduce blood pressure, as sartans also do, but by protecting and potentiating the kinins, they can reduce morbidity and mortality and improve the quality of life for patients with CVDs. This paper provides a brief review of the literature on this topic.

scholarly journals Angiotensin-(1-7): Translational Avenues in Cardiovascular Control

2019 ◽  
Vol 32 (12) ◽  
pp. 1133-1142 ◽  
Author(s):  
Daniela Medina ◽  
Amy C Arnold
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Current Knowledge ◽  
Renin Angiotensin System ◽  
Cardiovascular Control ◽  
Biologically Active ◽  
Global Public Health ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Cardiovascular Actions

Abstract Despite decades of research and numerous treatment approaches, hypertension and cardiovascular disease remain leading global public health problems. A major contributor to regulation of blood pressure, and the development of hypertension, is the renin-angiotensin system. Of particular concern, uncontrolled activation of angiotensin II contributes to hypertension and associated cardiovascular risk, with antihypertensive therapies currently available to block the formation and deleterious actions of this hormone. More recently, angiotensin-(1–7) has emerged as a biologically active intermediate of the vasodilatory arm of the renin-angiotensin system. This hormone antagonizes angiotensin II actions as well as offers antihypertensive, antihypertrophic, antiatherogenic, antiarrhythmogenic, antifibrotic and antithrombotic properties. Angiotensin-(1–7) elicits beneficial cardiovascular actions through mas G protein-coupled receptors, which are found in numerous tissues pivotal to control of blood pressure including the brain, heart, kidneys, and vasculature. Despite accumulating evidence for favorable effects of angiotensin-(1–7) in animal models, there is a paucity of clinical studies and pharmacokinetic limitations, thus limiting the development of therapeutic agents to better understand cardiovascular actions of this vasodilatory peptide hormone in humans. This review highlights current knowledge on the role of angiotensin-(1–7) in cardiovascular control, with an emphasis on significant animal, human, and therapeutic research efforts.

Cardiovascular hypertrophy in diabetic spontaneously hypertensive rats: optimizing blockade of the renin–angiotensin system

2003 ◽  
Vol 104 (4) ◽  
pp. 341-347 ◽  
Author(s):  
Markus LASSILA ◽  
Belinda J. DAVIS ◽  
Terri J. ALLEN ◽  
Louise M. BURRELL ◽  
Mark E. COOPER ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Calcium Channel ◽  
Spontaneously Hypertensive Rats ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Renin Angiotensin

The aim of the present study was to compare the antihypertrophic effects of blockade of the renin–angiotensin system (RAS), vasopeptidase inhibition and calcium channel antagonism on cardiac and vascular hypertrophy in diabetic spontaneously hypertensive rats (SHR). SHR with streptozotocin-induced diabetes were treated with one of the following therapies for 32 weeks: the angiotensin-converting enzyme (ACE) inhibitor captopril (100mg/kg); the angiotensin AT1 receptor antagonist valsartan (30mg/kg); a combination of captopril with valsartan; the vasopeptidase inhibitor mixanpril (100mg/kg); or the calcium channel antagonist amlodipine (6mg/kg). Systolic blood pressure and cardiac and mesenteric artery hypertrophy were assessed. Mean systolic blood pressure in diabetic SHR (200±5mmHg) was reduced by captopril (162±5mmHg), valsartan (173±5mmHg), mixanpril (176±2mmHg) and amlodipine (159±4mmHg), and was further reduced by the combination of captopril with valsartan (131±5mmHg). Captopril, valsartan and mixanpril reduced heart and left ventricle weights by approx. 10%. The combination of captopril and valsartan further reduced heart weight (-24%) and left ventricular weight (-29%). Amlodipine did not affect cardiac hypertrophy. Only mixanpril and the combination of captopril and valsartan significantly reduced mesenteric weight. The mesenteric wall/lumen ratio was reduced by all drugs, and to a greater extent by the combination of captopril and valsartan. We conclude that optimizing the blockade of vasoconstrictive pathways such as the RAS, particularly with the combination of ACE inhibition and AT1 receptor antagonism, is associated with antitrophic effects in the context of diabetes and hypertension. In contrast, calcium channel blockade, despite similar effects on blood pressure, confers less antitrophic effects in the diabetic heart and blood vessels.

scholarly journals From Rat to Human: Regulation of Renin-Angiotensin System Genes by Sry

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Jeremy W. Prokop ◽  
Ingrid Kazue Mizuno Watanabe ◽  
Monte E. Turner ◽  
Adam C. Underwood ◽  
Almir S. Martins ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Amino Acid ◽  
Promoter Activity ◽  
Renin Angiotensin System ◽  
Pressure Variation ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Blood Pressure Variation ◽  
Testis Determination

The testis determining protein, Sry, has functions outside of testis determination. Multiple Sry loci are found on the Y-chromosome. Proteins from these loci have differential activity on promoters of renin-angiotensin system genes, possibly contributing to elevation of blood pressure. Variation at amino acid 76 accounts for the majority of differential effects by rat proteins Sry1 and Sry3. Human SRY regulated rat promoters in the same manner as rat Sry, elevatingAgt, Ren, andAcepromoter activity while downregulatingAce 2. Human SRY significantly regulated human promoters ofAGT, REN, ACE2, AT2,andMAScompared to control levels, elevatingAGTandRENpromoter activity while decreasingACE2, AT2,andMAS. While the effect of human SRY on individual genes is often modest, we show that many different genes participating in the renin-angiotensin system can be affected by SRY, apparently in coordinated fashion, to produce more Ang II and less Ang-(1–7).

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