scholarly journals Increased angiotensin II formation in the brain modulates cardiovascular homeostasis and erythropoiesis

2021 ◽  
Author(s):  
André Felipe Rodrigues ◽  
Mihail Todiras ◽  
Fatimunnisa Qadri ◽  
Maria Jose Campagnole-Santos ◽  
Natalia Alenina ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Normal Fluid ◽  
Angiotensin System ◽  
Transgenic Mouse Line ◽  
Cardiovascular Homeostasis ◽  
The Brain

In spite of the fact that the modulatory effects of angiotensin II (Ang II) on the sympathetic nerve activity to targeted organs involved in blood pressure (BP) regulation is well acknowledged, the local production of this peptide in the brain and the consequences of enhanced central Ang II beyond the cardiovascular system are not yet well comprehended. In this study, we generated and validated a new transgenic mouse line overexpressing the rat full-length angiotensinogen (Agt) protein specifically in the brain (Agt-Tg). Adult Agt-Tg mice presented overall increased gene expression of total Agt in the brain including brainstem and hypothalamus. In addition, the excess of Agt led to abundantly detectable brain Ang II levels as well as increased circulating copeptin levels. Agt-Tg displayed raised BP in acute recordings, while long-term telemetrically measured basal BP was indistinguishable from wildtypes. Agt-Tg has altered peripheral renin angiotensin system and vasomotor sympathetic tone homeostasis, because renal gene expression analysis, plasma Ang II measurements and ganglionic blockade experiments revealed suppressed renin expression, reduced Ang II and higher neurogenic pressure response, respectively. Plasma and urine screens revealed apparently normal fluid and electrolyte handling in Agt-Tg. Interestingly, hematological analyses showed increased hematocrit in Agt-Tg caused by enhanced erythropoiesis, which was reverted by submitting the transgenic mice to a long-term peripheral sympathectomy protocol. Collectively, our findings suggest that Agt-Tg is a valuable tool not only to study brain Ang II formation and its modulatory effects on cardiovascular homeostasis but also its role in erythropoiesis control via autonomic modulation.

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.

scholarly journals Central AT1 receptor signaling by circulating angiotensin II is permissive to acute intermittent hypoxia-induced sympathetic neuroplasticity

2020 ◽  
Vol 128 (5) ◽  
pp. 1329-1337
Author(s):  
Caroline G. Shimoura ◽  
Mary Ann Andrade ◽  
Glenn M. Toney
Keyword(s):  
Angiotensin Ii ◽  
Intermittent Hypoxia ◽  
Renin Angiotensin System ◽  
Time Dependent ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Angiotensin System ◽  
Ras Activation ◽  
Long Term Facilitation

Acute intermittent hypoxia (AIH) triggers sympathetic long-term facilitation (sLTF) that relies on peripheral renin-angiotensin system (RAS) activation. Here, increasing AIH cycles from 5 to 10 proportionally increased RAS activity, but not the magnitude of post-AIH sLTF. Brain angiotensin II (ANG II) receptor blockade and nephrectomy each largely prevented sLTF, whereas central ANG II rescued it following nephrectomy. Peripheral RAS activation by AIH induces time-dependent neuroplasticity at an apparent central ANG II signaling threshold, triggering a stereotyped sLTF response.

Losartan and Angiotensin II Inhibit Aldosterone Production in Anephric Rats via Different Actions on the Intraadrenal Renin-Angiotensin System*

Endocrinology ◽  
1999 ◽  
Vol 140 (2) ◽  
pp. 675-682 ◽  
Author(s):  
Jörg Peters ◽  
Nicholas Obermüller ◽  
Alexander Woyth ◽  
Barbara Peters ◽  
Christiane Maser-Gluth ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Latency Period ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Relative Contribution ◽  
Aldosterone Production

Abstract Angiotensin II (ANG II) is a major stimulator of aldosterone biosynthesis. When investigating the relative contribution of circulating and locally produced ANG II, we were therefore surprised to find that ANG II, given chronically sc (200 ng/kg·min), markedly inhibits a nephrectomy (NX)-induced rise of aldosterone concentrations (from 10 ± 2 to 465 ± 90 ng/100 ml in vehicle infused, and from 9 ± 2 to 177 ± 35 in ANG II infused rats 55 h after NX and hemodialysis). We further observed, by in situ hybridization, that bilateral NX increases the number of adrenocortical cells expressing renin and that this rise was prevented by ANG II. Moreover, the rise of aldosterone levels was also inhibited by the AT1-receptor antagonist, losartan (10 μg/kg·min, chronically ip from 8 ± 2 to 199 ± 26 ng/100 ml), despite the absence of circulating renin and a reduction of ANG I to less than 10%. These data demonstrate that aldosterone production, after NX, is regulated by an intraadrenal renin-angiotensin system and that this system is physiologically suppressed by circulating angiotensin. Because the effects of losartan or ANG II on aldosterone production involved a latency period of at least 30 h after NX and were associated with a modulation or recruitment of renin-producing cells, we suggest that the intraadrenal renin-angiotensin system operates via regulation of cell differentiation on a long-term scale, rather than or additionally to its short-term effects on aldosterone synthase activity.

scholarly journals Intracrine angiotensin II functions originate from noncanonical pathways in the human heart

2016 ◽  
Vol 311 (2) ◽  
pp. H404-H414 ◽  
Author(s):  
Carlos M. Ferrario ◽  
Sarfaraz Ahmad ◽  
Jasmina Varagic ◽  
Che Ping Cheng ◽  
Leanne Groban ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Functional Significance ◽  
Vascular Remodeling ◽  
Human Heart ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Extended Form ◽  
Angiotensin I ◽  
Angiotensin System ◽  
Ras Genes

Although it is well-known that excess renin angiotensin system (RAS) activity contributes to the pathophysiology of cardiac and vascular disease, tissue-based expression of RAS genes has given rise to the possibility that intracellularly produced angiotensin II (Ang II) may be a critical contributor to disease processes. An extended form of angiotensin I (Ang I), the dodecapeptide angiotensin-(1–12) [Ang-(1–12)], that generates Ang II directly from chymase, particularly in the human heart, reinforces the possibility that an alternative noncanonical renin independent pathway for Ang II formation may be important in explaining the mechanisms by which the hormone contributes to adverse cardiac and vascular remodeling. This review summarizes the work that has been done in evaluating the functional significance of Ang-(1–12) and how this substrate generated from angiotensinogen by a yet to be identified enzyme enhances knowledge about Ang II pathological actions.

Thermal responses to central angiotensin II, SQ 20881, and dopamine infusions in sheep

1985 ◽  
Vol 248 (3) ◽  
pp. R371-R377 ◽  
Author(s):  
B. S. Huang ◽  
M. J. Kluger ◽  
R. L. Malvin
Keyword(s):  
Angiotensin Ii ◽  
Body Temperature ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Significant Rise ◽  
Ang Ii ◽  
Deep Body Temperature ◽  
Angiotensin System ◽  
Conscious Sheep

The thermoregulatory role of brain angiotensin II (ANG II) was tested by intracerebroventricular (IVT) infusion of ANG II or the converting enzyme inhibitor SQ 20881 (SQ) in 15 conscious sheep. Deep body temperature decreased 0.30 +/- 0.07 degree C (SE) during the 3-h period of IVT ANG II (25 ng/min) infusion (P less than 0.05) and increased 0.50 +/- 0.13 degree C during IVT SQ (1 microgram/min) infusion (P less than 0.01). To determine whether the rise in body temperature after IVT SQ infusion might be the result of a central renin-angiotensin system (RAS), SQ was infused IVT in five conscious sheep 20 h after bilateral nephrectomy. This resulted in a significant rise in body temperature of 0.28 +/- 0.05 degree C (P less than 0.05). When vasopressin antidiuretic hormone (ADH) was infused intravenously at the same time of IVT SQ infusion, the rise in temperature was depressed, but ADH did not lower the temperature below basal. IVT dopamine (20 micrograms/min) increased body temperature by 0.40 +/- 0.04 degree C (P less than 0.01), which was qualitatively similar to the result with IVT SQ. These data support the hypothesis that endogenous brain ANG II may play a role in thermoregulation. Furthermore, plasma ADH level, regulated in part by brain ANG II, is probably not the mediator of that thermoregulation. The similar effects of IVT dopamine and SQ on body temperature strengthen the hypothesis that dopamine may be involved in the central action of brain ANG II.

Central effects of angiotensin II and dopamine in sodium-depleted sheep

1985 ◽  
Vol 248 (5) ◽  
pp. R541-R548
Author(s):  
B. S. Huang ◽  
R. L. Malvin ◽  
R. J. Grekin
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Angiotensin System ◽  
Aldosterone Level ◽  
Central Effects ◽  
Dopaminergic Pathway

The effects of intracerebroventricular (IVT) infusion of angiotensin II (ANG II), the converting enzyme inhibitor SQ 20881, and dopamine were studied in 15 conscious Na-depleted sheep. IVT ANG II (25 ng/min) significantly increased plasma aldosterone (163 +/- 24%) and vasopressin (ADH) (533 +/- 100%). Plasma renin activity (PRA) was decreased to 64 +/- 10% of basal. IVT SQ (1 microgram/min) decreased aldosterone to 70 +/- 10% and ADH to 55 +/- 9% of basal. PRA increased to 124 +/- 10%. There were no significant changes in plasma Na, K, or cortisol levels nor in mean arterial or intracranial pressure after either infusion. Increasing the dose of SQ to 10 micrograms/min resulted in an increased magnitude of change in the same variables. IVT SQ (1 microgram/min) significantly decreased aldosterone level in five nephrectomized sheep. The responses to IVT dopamine (20 micrograms/min) were qualitatively similar to those elicited by IVT SQ. These data support the existence of an endogenous brain renin-angiotensin system (RAS) independent of the renal RAS. ANG II acts centrally to regulate plasma ADH, aldosterone, and PRA levels. The similarity of the responses to SQ and dopamine suggests that a dopaminergic pathway may be involved in these responses.

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.

Natriuretic response to renal interstitial hydrostatic pressure during angiotensin II blockade

1994 ◽  
Vol 266 (1) ◽  
pp. F117-F119 ◽  
Author(s):  
J. A. Haas ◽  
J. C. Lockhart ◽  
T. S. Larson ◽  
T. Henrikson ◽  
F. G. Knox
Keyword(s):  
Angiotensin Ii ◽  
Hydrostatic Pressure ◽  
Sodium Excretion ◽  
Renin Angiotensin System ◽  
Urinary Sodium Excretion ◽  
Treated Group ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Angiotensin System ◽  
Before And After

Increases in renal interstitial hydrostatic pressure (RIHP) increase urinary sodium excretion (UNaV). Experimentally increasing RIHP by direct renal interstitial volume expansion (DRIVE) has been shown to decrease proximal tubule sodium reabsorption. The purpose of the present study was to investigate whether the renin-angiotensin system modulates the natriuretic response to DRIVE. Unilateral nephrectomy and implantation of two polyethylene matrices were performed 3 wk before the acute experiment. Fractional sodium excretion (FENa), RIHP, and glomerular filtration rate (GFR) were measured before and after DRIVE in control rats (n = 9) and in rats receiving the angiotensin II (ANG II) receptor antagonist, losartan potassium (10 mg/kg i.v.; n = 10). DRIVE was achieved by infusing 100 microliters of 2.5% albumin solution directly into the renal interstitium. GFR remained unchanged by DRIVE in both groups. In control animals, DRIVE significantly increased both RIHP (delta 3.8 +/- 0.5 mmHg) and FENa (delta 0.92 +/- 0.19%). In the losartan-treated group, RIHP (delta 2.8 +/- 0.4 mmHg) and FENa (delta 1.93 +/- 0.41%) also significantly increased. The natriuretic response to DRIVE was significantly enhanced during ANG II receptor blockade compared with control animals (delta UNaV/delta RIHP = 2.01 +/- 0.67 vs. 0.44 +/- 0.17 mu eq.min-1 x mmHg-1, respectively; P < 0.05). These results suggest that the blockade of angiotensin enhances the natriuretic response to increased RIHP during DRIVE.

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