scholarly journals The Renin–Angiotensin System Modulates Dopaminergic Neurotransmission: A New Player on the Scene

2021 ◽  
Vol 13 ◽  
Author(s):  
Tamara Kobiec ◽  
Matilde Otero-Losada ◽  
Guenson Chevalier ◽  
Lucas Udovin ◽  
Sofía Bordet ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Dopaminergic Neurons ◽  
Neuronal Degeneration ◽  
Renin Angiotensin System ◽  
Receptor Activation ◽  
World Population ◽  
Major Health Problem ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Brain

Parkinson’s disease (PD) is an extrapyramidal disorder characterized by neuronal degeneration in several regions of the peripheral and central nervous systems. It is the second most frequent neurodegenerative disease after Alzheimer’s. It has become a major health problem, affecting 1% of the world population over 60 years old and 3% of people beyond 80 years. The main histological findings are intracellular Lewy bodies composed of misfolded α-synuclein protein aggregates and loss of dopaminergic neurons in the central nervous system. Neuroinflammation, apoptosis, mitochondrial dysfunction, altered calcium homeostasis, abnormal protein degradation, and synaptic pathobiology have been put forward as mechanisms leading to cell death, α-synuclein deposition, or both. A progressive loss of dopaminergic neurons in the substantia nigra late in the neurodegeneration leads to developing motor symptoms like bradykinesia, tremor, and rigidity. The renin–angiotensin system (RAS), which is involved in regulating blood pressure and body fluid balance, also plays other important functions in the brain. The RAS is involved in the autocrine and paracrine regulation of the nigrostriatal dopaminergic synapses. Dopamine depletion, as in PD, increases angiotensin II expression, which stimulates or inhibits dopamine synthesis and is released via AT1 or AT2 receptors. Furthermore, angiotensin II AT1 receptors inhibit D1 receptor activation allosterically. Therefore, the RAS may have an important modulating role in the flow of information from the brain cortex to the basal ganglia. High angiotensin II levels might even aggravate neurodegeneration, activating the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, which leads to increased reactive oxygen species production.

Role of the renin-angiotensin system in the pathogenesis of preeclampsia

2005 ◽  
Vol 288 (4) ◽  
pp. F614-F625 ◽  
Author(s):  
Dinesh M. Shah
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Receptor Activation ◽  
Gravid Uterus ◽  
Type I ◽  
Hypertensive Disorder ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Organ Systems

Preeclampsia is a hypertensive disorder unique to pregnancy with consistent involvement of the kidney. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of preeclampsia. In the gravid state, in addition to the RAS in the kidney, there is a tissue-based RAS in the uteroplacental unit. Increased renin expression observed both in human preeclampsia and in a transgenic mouse model with a human preeclampsia-like syndrome supports the concept that activation of the uteroplacental RAS, with angiotensin II entering the systemic circulation, may mediate the pathogenesis of preeclampsia. A novel disease paradigm of the two-kidney one-clip (2K-1C) Goldblatt model is presented for preeclampsia, wherein the gravid uterus is the clipped “kidney” and the two maternal kidneys represent the unclipped kidney. Validation of the 2K-1C Goldblatt model analogy requires evidence of elevated angiotensin II in the peripheral circulation before vascular maladaptation in preeclampsia. Convincing evidence of the elevation of angiotensin II in preeclampsia does not exist despite the fact that much of vascular pathogenesis appears to be due to angiotensin type I (AT1) receptor activation. Vascular maladaptation with increased vasomotor tone, endothelial dysfunction, and increased sensitivity to angiotensin II and norepinephrine in manifest preeclampsia may be explained on the basis of angiotensin II-mediated mechanisms. Recently, novel angiotensin II-related biomolecular mechanisms have been described in preeclampsia. These include AT1and bradykinin B2receptor heterodimerization and the production of an autoantibody against AT1. Various organ systems with a predilection for involvement in preeclampsia are each a site of a tissue-based RAS. How angiotensin II-mediated mechanisms may explain the primary clinical-pathological features of preeclampsia is described. Future investigations are proposed to more precisely define the role of activation of the uteroplacental RAS in the mechanisms underlying preeclampsia.

scholarly journals The Brain Renin-Angiotensin System Modulates Angiotensin II–Induced Hypertension and Cardiac Hypertrophy

Hypertension ◽  
2000 ◽  
Vol 35 (1) ◽  
pp. 409-412 ◽  
Author(s):  
Ovidiu Baltatu ◽  
José Antonio Silva ◽  
Detlev Ganten ◽  
Michael Bader
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Induced Hypertension ◽  
The Brain

Central interaction of the brain atrial natriuretic polypeptide (ANP) system and the brain rennin–angiotensin system in ANP secretion from heart—evidence for possible brain–heart axis

1988 ◽  
Vol 66 (3) ◽  
pp. 255-261 ◽  
Author(s):  
Hiroshi Itoh ◽  
Kazuwa Nakao ◽  
Takayuki Yamada ◽  
Narito Morii ◽  
Shozo Shiono ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Intracerebroventricular Administration ◽  
Volume Loading ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Atrial Natriuretic Polypeptide ◽  
Basal Plasma ◽  
The Brain ◽  
Atrial Natriuretic

To elucidate the involvement of the brain renin–angiotensin system and the brain atrial natriuretic polypeptide (ANP) system in the regulation of ANP secretion from the heart, the effects of intracerebroventricular administration of angiotensin II and ANP on the plasma ANP level were examined in conscious unrestrained rats. The intracerebroventricular administration of angiotensin II at doses of 100 ng and 1 μg significantly enhanced ANP secretion induced by volume-loading with 3-mL saline infusion (peak values of the plasma ANP level: control, 220 ± 57 pg/mL; 100 ng angiotensin II, 1110 ± 320 pg/mL, p < 0.01; 1 μg angiotensin II, 1055 ± 60 pg/mL, p < 0.01). The intracerebroventricular injection of angiotensin II at the same doses alone had no significant effect on the basal plasma ANP level. The enhancing effect of central angiotensin II on ANP secretion induced by volume-loading was significantly attenuated by pretreatment with the intravenous administration of the V1-receptor antagonist of vasopressin or with the intracerebroventricular administration of phentolamine. The intracerebroventricular administration of α-rANP(4–28) (5 μg) had no significant influence on the basal plasma ANP level; however, it significantly attenuated central angiotensin II potentiating effect of volume-loading induced ANP secretion. These results indicate that the brain rennin–angiotensin system regulates ANP secretion via the stimulation of vasopressin secretion and (or) via the activation of the central α-adrenergic neural pathway, and that the brain ANP system interacts with the brain renin–angiotensin system in the central modulation of ANP secretion from the heart. The result further supports the proposed antagonistic relationship between the brain ANP system and the brain renin–angiotensin system in body fluid and blood pressure homeostasis.

scholarly journals Activation of the Central Renin-Angiotensin System Causes Local Cerebrovascular Dysfunction

Stroke ◽  
2021 ◽  
Author(s):  
T. Michael De Silva ◽  
Mary L. Modrick ◽  
Justin L. Grobe ◽  
Frank M. Faraci
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Cerebral Arteries ◽  
Renin Angiotensin System ◽  
Mesenteric Arteries ◽  
Common Mechanism ◽  
Brain Health ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Brain

Background and Purpose: Hypertension is a leading risk factor for cerebrovascular disease and loss of brain health. While the brain renin-angiotensin system (RAS) contributes to hypertension, its potential impact on the local vasculature is unclear. We tested the hypothesis that activation of the brain RAS would alter the local vasculature using a modified deoxycorticosterone acetate (DOCA) model. Methods: C57BL/6 mice treated with DOCA (50 mg SQ; or shams) were given tap H 2 O and H 2 O with 0.9% NaCl for 1 to 3 weeks. Results: In isolated cerebral arteries and parenchymal arterioles from DOCA-treated male mice, endothelium- and nitric oxide-dependent dilation was progressively impaired, while mesenteric arteries were unaffected. In contrast, cerebral endothelial function was not significantly affected in female mice treated with DOCA. In males, mRNA expression of renal Ren1 was markedly reduced while RAS components (eg, Agt and Ace ) were increased in both brain and cerebral arteries with central RAS activation. In NZ44 reporter mice expressing GFP (green fluorescent protein) driven by the angiotensin II type 1A receptor ( Agtr1a ) promoter, DOCA increased GFP expression ≈3-fold in cerebral arteries. Impaired endothelial responses were restored to normal by losartan, an AT1R (angiotensin II type 1 receptor) antagonist. Last, DOCA treatment produced inward remodeling of parenchymal arterioles. Conclusions: These findings suggest activation of the central and cerebrovascular RAS impairs endothelial (nitric oxide dependent) signaling in brain through expression and activation of AT1R and sex-dependent effects. The central RAS may be a key contributor to vascular dysfunction in brain in a preclinical (low renin) model of hypertension. Because the brain RAS is also activated during aging and other diseases, a common mechanism may promote loss of endothelial and brain health despite diverse cause.

scholarly journals A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity

2012 ◽  
Vol 303 (2) ◽  
pp. H197-H206 ◽  
Author(s):  
Aline M. Hilzendeger ◽  
Donald A. Morgan ◽  
Leonard Brooks ◽  
David Dellsperger ◽  
Xuebo Liu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Food Intake ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Renin Angiotensin System ◽  
Melanocortin Receptor ◽  
Nerve Activity ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Brain

The sympathetic nervous system, leptin, and renin-angiotensin system (RAS) have been implicated in obesity-associated hypertension. There is increasing evidence for the presence of both leptin and angiotensin II receptors in several key brain cardiovascular and metabolic control regions. We tested the hypothesis that the brain RAS plays a facilitatory role in the sympathetic nerve responses to leptin. In rats, intracerebroventricular (ICV) administration of losartan (5 μg) selectively inhibited increases in renal and brown adipose tissue (BAT) sympathetic nerve activity (SNA) produced by leptin (10 μg ICV) but did not reduce the SNA responses to corticotrophin-releasing factor (CRF) or the melanocortin receptor agonist MTII. In mice with deletion of angiotensin II type-1a receptors (AT1aR−/−), increases in renal and BAT SNA induced by leptin (2 μg ICV) were impaired whereas SNA responses to MTII were preserved. Decreases in food intake and body weight with ICV leptin did not differ in AT1aR−/− vs. AT1aR+/+ mice. ICV leptin in rats increased AT1aR and angiotensin-converting enzyme (ACE) mRNA in the subfornical organ and AT1aR mRNA in the arcuate nucleus, suggesting leptin-induced upregulation of the brain RAS in specific brain regions. To evaluate the role of de novo production of brain angiotensin II in SNA responses to leptin, we treated rats with captopril (12.5 μg ICV). Captopril attenuated leptin effects on renal and BAT SNA. In conclusion, these studies provide evidence that the brain RAS selectively facilitates renal and BAT sympathetic nerve responses to leptin while sparing effects on food intake.

scholarly journals The Angiotensin II Type 2 Receptor in Brain Functions: An Update

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Marie-Odile Guimond ◽  
Nicole Gallo-Payet
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Brain Functions ◽  
Physiological Relevance ◽  
Ang Iv ◽  
The Brain

Angiotensin II (Ang II) is the main active product of the renin-angiotensin system (RAS), mediating its action via two major receptors, namely, the Ang II type 1 (AT1) receptor and the type 2 (AT2) receptor. Recent results also implicate several other members of the renin-angiotensin system in various aspects of brain functions. The first aim of this paper is to summarize the current state of knowledge regarding the properties and signaling of the AT2receptor, its expression in the brain, and its well-established effects. Secondly, we will highlight the potential role of the AT2receptor in cognitive function, neurological disorders and in the regulation of appetite and the possible link with development of metabolic disorders. The potential utility of novel nonpeptide selective AT2receptor ligands in clarifying potential roles of this receptor in physiology will also be discussed. If confirmed, these new pharmacological tools should help to improve impaired cognitive performance, not only through its action on brain microcirculation and inflammation, but also through more specific effects on neurons. However, the overall physiological relevance of the AT2receptor in the brain must also consider the Ang IV/AT4receptor.

Actions of angiotensin II on the brain: mechanisms and physiologic role

1984 ◽  
Vol 246 (5) ◽  
pp. F533-F543 ◽  
Author(s):  
I. A. Reid
Keyword(s):  
Angiotensin Ii ◽  
Large Body ◽  
Renin Angiotensin System ◽  
Circumventricular Organs ◽  
Acth Stimulation ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Arterial Blood ◽  
Receptor Sites ◽  
The Brain

Angiotensin II acts on the brain to produce a variety of effects including elevation of arterial blood pressure, increased release of vasopressin and ACTH, stimulation of drinking and sodium appetite, and natriuresis. Many, and possibly all, of these effects can be produced by centrally administered angiotensin II or by circulating angiotensin II, which appear to act at common receptor sites located in the circumventricular organs. Whether these effects are normally produced by blood-borne angiotensin II formed by the renal renin-angiotensin system, by angiotensin II formed centrally by the putative brain renin-angiotensin system, or by both, remains to be determined. A large body of information concerning the site and mechanism of these different central actions of angiotensin II is available, and the physiologic significance of these actions is beginning to be understood. Nevertheless, much additional research will be required before the actions of angiotensin II on the brain are completely understood.

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