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 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.

scholarly journals Nuclear angiotensin II type 2 (AT2) receptors are functionally linked to nitric oxide production

2009 ◽  
Vol 296 (6) ◽  
pp. F1484-F1493 ◽  
Author(s):  
TanYa M. Gwathmey ◽  
Hossam A. Shaltout ◽  
Karl D. Pendergrass ◽  
Nancy T. Pirro ◽  
Jorge P. Figueroa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Molecular Form ◽  
Rat Kidney ◽  
Renin Angiotensin System ◽  
Receptor Subtypes ◽  
No Production ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

Expression of nuclear angiotensin II type 1 (AT1) receptors in rat kidney provides further support for the concept of an intracellular renin-angiotensin system. Thus we examined the cellular distribution of renal ANG II receptors in sheep to determine the existence and functional roles of intracellular ANG receptors in higher order species. Receptor binding was performed using the nonselective ANG II antagonist 125I-[Sar1,Thr8]-ANG II (125I-sarthran) with the AT1 antagonist losartan (LOS) or the AT2 antagonist PD123319 (PD) in isolated nuclei (NUC) and plasma membrane (PM) fractions obtained by differential centrifugation or density gradient separation. In both fetal and adult sheep kidney, PD competed for the majority of cortical NUC (≥70%) and PM (≥80%) sites while LOS competition predominated in medullary NUC (≥75%) and PM (≥70%). Immunodetection with an AT2 antibody revealed a single ∼42-kDa band in both NUC and PM extracts, suggesting a mature molecular form of the NUC receptor. Autoradiography for receptor subtypes localized AT2 in the tubulointerstitium, AT1 in the medulla and vasa recta, and both AT1 and AT2 in glomeruli. Loading of NUC with the fluorescent nitric oxide (NO) detector DAF showed increased NO production with ANG II (1 nM), which was abolished by PD and N-nitro-l-arginine methyl ester, but not LOS. Our studies demonstrate ANG II receptor subtypes are differentially expressed in ovine kidney, while nuclear AT2 receptors are functionally linked to NO production. These findings provide further evidence of a functional intracellular renin-angiotensin system within the kidney, which may represent a therapeutic target for the regulation of blood pressure.

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 Interactions between local renin angiotensin system and nitric oxide in the brain of Trypanosoma cruzi infected rats

Acta Tropica ◽  
2019 ◽  
Vol 194 ◽  
pp. 36-40 ◽  
Author(s):  
Aline Silva Miranda ◽  
Milene Alvarenga Rachid ◽  
Cássio Ferraz Souza ◽  
Bruna da Silva Oliveira ◽  
Rodrigo Novaes Ferreira ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Trypanosoma Cruzi ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Brain

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.

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