scholarly journals Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Yavuz Beyazit ◽  
Tugrul Purnak ◽  
Gulay Sain Guven ◽  
Ibrahim C. Haznedaroglu
Keyword(s):  
Bone Marrow ◽  
Renin Angiotensin System ◽  
Cellular Growth ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Local Bone ◽  
Growth Production ◽  
And Function

Local hematopoietic bone marrow (BM) renin-angiotensin system (RAS) affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II), the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R), has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis.

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 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.

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 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.

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