scholarly journals Alterations of the renin-angiotensin system at the RVLM of transgenic rats with low brain angiotensinogen

2001 ◽  
Vol 280 (2) ◽  
pp. R428-R433 ◽  
Author(s):  
Ovidiu Baltatu ◽  
Marco A. P. Fontes ◽  
Maria J. Campagnole-Santos ◽  
Sordaine Caligiorni ◽  
Detlev Ganten ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Mean ◽  
Low Levels

The transgenic rats TGR(ASrAOGEN) (TGR) with low levels of brain angiotensinogen were analyzed for cardiovascular reactivity to microinjections of ANG II and angiotensin receptor (AT1) antagonists [CV-11974, AT1 specific; A-779, ANG-(1–7) selective; sarthran, nonspecific] into the rostral ventrolateral medulla (RVLM) of conscious rats. Microinjection of ANG II resulted in a significantly higher increase in the mean arterial pressure (MAP) of TGR than control [Sprague-Dawley (SD)] rats, suggesting an upregulation of ANG II receptors in TGR. CV-11974 produced an increase in MAP of SD but not in TGR rats. A-779 produced a depressor response in SD but not in TGR rats. Conversely, sarthran produced a similar decrease of MAP in both rat groups. The pressor effect of the AT1 antagonist may indicate an inhibitory role of AT1 receptors in the RVLM. On the other hand, ANG-(1–7) appears to have a tonic excitatory role in this region. The altered response to specific angiotensin antagonists in TGR further supports the functionally relevant decrease in angiotensins in the brains of TGR and corroborates the importance of the central renin-angiotensin system in cardiovascular homeostasis.

Peripheral and central angiotensin II regulates expression of genes of the renin-angiotensin system

1992 ◽  
Vol 262 (5) ◽  
pp. E651-E657 ◽  
Author(s):  
K. Kohara ◽  
K. B. Brosnihan ◽  
C. M. Ferrario ◽  
A. Milsted
Keyword(s):  
Northern Blot Analysis ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Expression Of Genes ◽  
Sprague Dawley Rats ◽  
Renin Mrna ◽  
Lower Brain Stem

We investigated whether angiotensin (ANG) II has the potential to regulate expression of genes of the renin-angiotensin system (RAS) in peripheral and central tissues. ANG II (0.1 or 6.0 nmol/h) was infused by osmotic minipump into male Sprague-Dawley rats (225-250 g) for 5 days, either intravenously or intracerebroventricularly. We measured angiotensinogen mRNA in liver, adrenal glands, and brain (hypothalamus and lower brain stem), renin mRNA in the kidney, and angiotensin-converting enzyme (ACE) mRNA in the lung and testis by Northern blot analysis. We demonstrated that plasma ANG II increases the levels of liver angiotensinogen mRNA, decreases kidney renin mRNA, and decreases lung ACE mRNA. Intracerebroventricular administration of ANG II resulted in a different pattern of responses of the peripheral RAS components. Liver angiotensinogen mRNA was increased, and kidney renin mRNA was decreased by both doses of ANG II, whereas lung ACE mRNA remained unresponsive at either dose. Centrally mediated influences of ANG II are most likely indirect since plasma ANG II concentration was not changed. This study has revealed that ANG II has profound diverse effects that influence the regulation of its formation. Further, results indicate that genes of the RAS responded to exogenous ANG II in both tissue- and route-specific ways.

Splanchnic blood flow and hepatic glucose production in exercising humans: role of renin-angiotensin system

2001 ◽  
Vol 281 (6) ◽  
pp. R1854-R1861 ◽  
Author(s):  
Raynald Bergeron ◽  
Michael Kjær ◽  
Lene Simonsen ◽  
Jens Bülow ◽  
Dorthe Skovgaard ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renin Angiotensin System ◽  
Glucose Production ◽  
Splanchnic Blood Flow ◽  
Control Group ◽  
Moderate Exercise ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O2 consumption (V˙o 2 max) followed by 30 min at 70% V˙o 2 maxeither with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an ∼20-fold increase ( P < 0.001) in ANG II levels in the control group (5.4 ± 1.0 to 102.0 ± 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 ± 1.2 to 13.2 ± 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, V˙o 2, and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 ± 0.12, ACE blockade; 1.59 ± 0.18 l/min, control) decreased during moderate exercise (0.78 ± 0.07, ACE blockade; 0.74 ± 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 ± 0.06, ACE blockade; 0.68 ± 0.10 mmol/min, control) increased during moderate exercise (1.97 ± 0.29, ACE blockade; 1.91 ± 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.

scholarly journals Role of the renin-angiotensin system in the development of severe COVID-19 in hypertensive patients

2020 ◽  
Vol 319 (4) ◽  
pp. L596-L602
Author(s):  
Rodrigo Pacheco Silva-Aguiar ◽  
Diogo Barros Peruchetti ◽  
Patricia Rieken Macedo Rocco ◽  
Alvin H. Schmaier ◽  
Patrícia Machado Rodrigues e Silva ◽  
...  
Keyword(s):  
Critical Role ◽  
Renin Angiotensin System ◽  
Multiple Organ ◽  
Ang Ii ◽  
Angiotensin System ◽  
Hypertensive Patients ◽  
Renin Angiotensin ◽  
Therapeutic Benefits ◽  
Global Threat

A new form of severe acute respiratory syndrome (SARS) caused by SARS-coronavirus 2 (CoV-2), called COVID-19, has become a global threat in 2020. The mortality rate from COVID-19 is high in hypertensive patients, making this association especially dangerous. There appears to be a consensus, despite the lack of experimental data, that angiotensin II (ANG II) is linked to the pathogenesis of COVID-19. This process may occur due to acquired deficiency of angiotensin-converting enzyme 2 (ACE2), resulting in reduced degradation of ANG II. Furthermore, ANG II has a critical role in the genesis and worsening of hypertension. In this context, the idea that there is a surge in the level of ANG II with COVID-19 infection, causing multiple organ injuries in hypertensive patients becomes attractive. However, the role of other components of the renin angiotensin system (RAS) in this scenario requires elucidation. The identification of other RAS components in COVID-19 hypertension may provide both diagnostic and therapeutic benefits. Here, we summarize the pathophysiologic contributions of different components of RAS in hypertension and their possible correlation with poor outcome observed in hypertensive patients with COVID-19.

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

2008 ◽  
Vol 294 (1) ◽  
pp. R26-R32 ◽  
Author(s):  
J. C. B. Ferreira ◽  
A. V. Bacurau ◽  
F. S. Evangelista ◽  
M. A. Coelho ◽  
E. M. Oliveira ◽  
...  
Keyword(s):  
Heart Failure ◽  
Renin Angiotensin System ◽  
Collagen Content ◽  
Ang Ii ◽  
Male Adult ◽  
Angiotensin System ◽  
Sympathetic Hyperactivity ◽  
Renin Angiotensin ◽  
Ras Activation

Sympathetic hyperactivity (SH) and renin angiotensin system (RAS) activation are commonly associated with heart failure (HF), even though the relative contribution of these factors to the cardiac derangement is less understood. The role of SH on RAS components and its consequences for the HF were investigated in mice lacking α2A and α2C adrenoceptor knockout (α2A/α2CARKO) that present SH with evidence of HF by 7 mo of age. Cardiac and systemic RAS components and plasma norepinephrine (PN) levels were evaluated in male adult mice at 3 and 7 mo of age. In addition, cardiac morphometric analysis, collagen content, exercise tolerance, and hemodynamic assessments were made. At 3 mo, α2A/α2CARKO mice showed no signs of HF, while displaying elevated PN, activation of local and systemic RAS components, and increased cardiomyocyte width (16%) compared with wild-type mice (WT). In contrast, at 7 mo, α2A/α2CARKO mice presented clear signs of HF accompanied only by cardiac activation of angiotensinogen and ANG II levels and increased collagen content (twofold). Consistent with this local activation of RAS, 8 wk of ANG II AT1 receptor blocker treatment restored cardiac structure and function comparable to the WT. Collectively, these data provide direct evidence that cardiac RAS activation plays a major role underlying the structural and functional abnormalities associated with a genetic SH-induced HF in mice.

scholarly journals The Prorenin and (Pro)renin Receptor: New Players in the Brain Renin-Angiotensin System?

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Wencheng Li ◽  
Hua Peng ◽  
Dale M. Seth ◽  
Yumei Feng
Keyword(s):  
Renin Angiotensin System ◽  
Ang Ii ◽  
Future Perspectives ◽  
Vasopressin Release ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Treatment Of Hypertension ◽  
High Level ◽  
The Brain

It is well known that the brain renin-angiotensin (RAS) system plays an essential role in the development of hypertension, mainly through the modulation of autonomic activities and vasopressin release. However, how the brain synthesizes angiotensin (Ang) II has been a debate for decades, largely due to the low renin activity. This paper first describes the expression of the vasoconstrictive arm of RAS components in the brain as well as their physiological and pathophysiological significance. It then focus on the (pro)renin receptor (PRR), a newly discovered component of the RAS which has a high level in the brain. We review the role of prorenin and PRR in peripheral organs and emphasize the involvement of brain PRR in the pathogenesis of hypertension. Some future perspectives in PRR research are heighted with respect to novel therapeutic target for the treatment of hypertension and other cardiovascular diseases.

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.

Pivotal role of the renin-angiotensin system in Lyon hypertensive rats

1997 ◽  
Vol 273 (5) ◽  
pp. R1793-R1799 ◽  
Author(s):  
Pierre Lantelme ◽  
Ming Lo ◽  
Laurent Luttenauer ◽  
Jean Sassard
Keyword(s):  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Adult Age ◽  
Enhanced Sensitivity ◽  
Regional Hemodynamics ◽  
Renal Vascular

We assessed the role of the renin-angiotensin system (RAS) in Lyon genetically hypertensive (LH) and normotensive (LN) rats by measuring 1) kidney renin and prorenin contents; 2) effects of early, prolonged angiotensin-converting enzyme (ACE) inhibition on blood pressure (BP) and regional hemodynamics; and 3) acute and chronic responses to angiotensin II (ANG II) and norepinephrine (NE). At the adult age, LH rats differed from LN rats by elevated BP, left ventricle weight, and vascular resistances, especially in the kidneys, associated with lower kidney renin and prorenin contents. ACE inhibition (perindopril, 3 mg ⋅ kg−1 ⋅ 24 h−1 orally from 3 to 15 wk of age) suppressed the development of hypertension, cardiac hypertrophy, and the increase in renal vascular resistances. No specific hypersensitivity to ANG II could be disclosed in acute conditions. In perindopril-treated LH rats, a 4-wk infusion of ANG II (200 ng ⋅ kg−1 ⋅ min−1) but not of NE (1,000 ng ⋅ kg−1 ⋅ min−1) restored hypertension, mimicked the hemodynamic alterations seen in untreated LH rats, and produced a brief sodium retention. It is concluded that in LH rats, despite a low basal renin secretion, hypertension and hemodynamic abnormalities 1) are fully dependent on an active RAS and 2) may involve an enhanced sensitivity to the chronic effects of ANG II.

Role of the renin-angiotensin system in the systemic microvascular inflammation of alveolar hypoxia

2007 ◽  
Vol 292 (5) ◽  
pp. H2285-H2294 ◽  
Author(s):  
Norberto C. Gonzalez ◽  
Julie Allen ◽  
Eric J. Schmidt ◽  
Alfred J. Casillan ◽  
Teresa Orth ◽  
...  
Keyword(s):  
Ace Inhibitor ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Alveolar Hypoxia ◽  
Microvascular Inflammation

Alveolar hypoxia (AH) induces widespread systemic inflammation. Previous studies have shown dissociation between microvascular Po2 and inflammation. Furthermore, plasma from AH rats (PAHR) induces mast cell (MC) activation, inflammation, and vasoconstriction in normoxic cremasters, while plasma from normoxic rats does not produce these responses. These results suggest that inflammation of AH is triggered by a blood-carried agent. This study investigated the involvement of the renin-angiotensin system (RAS) in the inflammation of AH. Both an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (ANG II) receptor blocker (ANG II RB) inhibited the leukocyte-endothelial adherence produced by AH, as well as the inflammation produced by PAHR in normoxic rat cremasters. MC stabilization with cromolyn blocked the effects of PAHR but not those of topical ANG II on normoxic cremasters, suggesting ANG II generation via MC activation by PAHR. This was supported by the observation that ACE inhibition and ANG II RB blocked the leukocyte-endothelial adherence produced by the MC secretagogue compound 48/80. These results suggest that the intermediary agent contained in PAHR activates MC and stimulates the RAS, leading to inflammation, and imply an RAS role in AH-induced inflammation.

Role of the renin-angiotensin system in drinking of seawater-adapted eels Anguilla japonica: a reevaluation

2000 ◽  
Vol 279 (3) ◽  
pp. R1105-R1111 ◽  
Author(s):  
Yoshio Takei ◽  
Takamasa Tsuchida
Keyword(s):  
Arterial Pressure ◽  
Plasma Osmolality ◽  
Renin Angiotensin System ◽  
Minor Role ◽  
Dependent Manner ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Arterial Blood

The role of ANG II, a potent dipsogenic hormone, in copious drinking of seawater eels was examined. SQ-14225 (SQ), an angiotensin-converting enzyme inhibitor, infused intra-arterially at 0.01–1 μg · kg−1 · min−1, depressed drinking and arterial blood pressure in a dose-dependent manner. The inhibition was accompanied by a small decrease in plasma ANG II concentration, which became significant at 1 μg · kg−1 · min−1. After the infusate was changed back to the vehicle, the depression of drinking and arterial pressure continued for >2 h, although plasma ANG II concentration rebounded above the level before SQ infusion. By contrast, infusion of anti-ANG II serum (0.01–1 μg · kg−1 · min−1) did not suppress drinking and arterial pressure, although plasma ANG II concentration decreased to undetectable levels. Plasma atrial natriuretic peptide and plasma osmolality, which influence drinking rate in eels, did not change during SQ or antiserum infusions. These results suggest that the renin-angiotensin system plays only a minor role in the vigorous drinking observed in seawater eels. The results also suggest that the antidipsogenic and vasodepressor effects of SQ in seawater eels are not due solely to the inhibition of ANG II formation in plasma.

scholarly journals The brain renin-angiotensin system and cardiovascular responses to stress: insights from transgenic rats with low brain angiotensinogen

2012 ◽  
Vol 113 (12) ◽  
pp. 1929-1936 ◽  
Author(s):  
Amy C. Arnold ◽  
Atsushi Sakima ◽  
Sherry O. Kasper ◽  
Sherry Vinsant ◽  
Maria Antonia Garcia-Espinosa ◽  
...  
Keyword(s):  
Stress Responses ◽  
Renin Angiotensin System ◽  
Cardiovascular Responses ◽  
Ang Ii ◽  
Transgenic Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Brain Peptides ◽  
The Impact ◽  
The Brain

The renin-angiotensin system (RAS) has been identified as an attractive target for the treatment of stress-induced cardiovascular disorders. The effects of angiotensin (ANG) peptides during stress responses likely result from an integration of actions by circulating peptides and brain peptides derived from neuronal and glial sources. The present review focuses on the contribution of endogenous brain ANG peptides to pathways involved in cardiovascular responses to stressors. During a variety of forms of stress, neuronal pathways in forebrain areas containing ANG II or ANG-(1–7) are activated to stimulate descending angiotensinergic pathways that increase sympathetic outflow to increase blood pressure. We provide evidence that glia-derived ANG peptides influence brain AT1 receptors. This appears to result in modulation of the responsiveness of the neuronal pathways activated during stressors that elevate circulating ANG peptides to activate brain pathways involving descending hypothalamic projections. It is well established that increased cardiovascular reactivity to stress is a significant predictor of hypertension and other cardiovascular diseases. This review highlights the importance of understanding the impact of RAS components from the circulation, neurons, and glia on the integration of cardiovascular responses to stressors.

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