Protective axis of the renin–angiotensin system in the brain

2014 ◽  
Vol 127 (5) ◽  
pp. 295-306 ◽  
Author(s):  
Mariela M. Gironacci ◽  
Flavia M. Cerniello ◽  
Nadia A. Longo Carbajosa ◽  
Jorge Goldstein ◽  
Bruno D. Cerrato
Keyword(s):  
Neuronal Apoptosis ◽  
Baroreflex Sensitivity ◽  
Potential Role ◽  
Renin Angiotensin System ◽  
Ventrolateral Medulla ◽  
Hypothalamic Area ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Brain

The RAS (renin–angiotensin system) is composed of two arms: the pressor arm containing AngII (angiotensin II)/ACE (angiotensin-converting enzyme)/AT1Rs (AngII type 1 receptors), and the depressor arm represented by Ang-(1–7) [angiotensin-(1–7)]/ACE2/Mas receptors. All of the components of the RAS are present in the brain. Within the brain, Ang-(1–7) contributes to the regulation of BP (blood pressure) by acting at regions that control cardiovascular function such that, when Ang-(1–7) is injected into the nucleus of the solitary tract, caudal ventrolateral medulla, paraventricular nucleus or anterior hypothalamic area, a reduction in BP occurs; however, when injected into the rostral ventrolateral medulla, Ang-(1–7) stimulates an increase in BP. In contrast with AngII, Ang-(1–7) improves baroreflex sensitivity and has an inhibitory neuromodulatory role in hypothalamic noradrenergic neurotransmission. Ang-(1–7) not only exerts effects related to BP regulation, but also acts as a cerebroprotective component of the RAS by reducing cerebral infarct size and neuronal apoptosis. In the present review, we provide an overview of effects elicited by Ang-(1–7) in the brain, which suggest a potential role for Ang-(1–7) in controlling the central development of hypertension.

scholarly journals Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system

2007 ◽  
Vol 292 (1) ◽  
pp. R373-R381 ◽  
Author(s):  
Marc F. Doobay ◽  
Lauren S. Talman ◽  
Teresa D. Obr ◽  
Xin Tian ◽  
Robin L. Davisson ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Neuron Specific Enolase ◽  
Neuronal Cell ◽  
Renin Angiotensin System ◽  
Brain Structures ◽  
Ventrolateral Medulla ◽  
Motor Nucleus ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Brain

Angiotensin-converting enzyme 2 (ACE2) is a newly discovered carboxy-peptidase responsible for the formation of vasodilatory peptides such as angiotensin-(1–7). We hypothesized that ACE2 is part of the brain renin-angiotensin system, and its expression is regulated by the other elements of this system. ACE2 immunostaining was performed in transgenic mouse brain sections from neuron-specific enolase-AT1A (overexpressing AT1A receptors), R+A+ (overexpressing angiotensinogen and renin), and control (nontransgenic littermates) mice. Results show that ACE2 staining is widely distributed throughout the brain. Using cell-type-specific antibodies, we observed that ACE2 staining is present in the cytoplasm of neuronal cell bodies but not in glial cells. In the subfornical organ, an area lacking the blood-brain barrier and sensitive to blood-borne angiotensin II, ACE2 was significantly increased in transgenic mice. Interestingly, ACE2 mRNA and protein expression were inversely correlated in the nucleus of tractus solitarius/dorsal motor nucleus of the vagus and the ventrolateral medulla, when comparing transgenic to nontransgenic mice. These results suggest that ACE2 is localized to the cytoplasm of neuronal cells in the brain and that ACE2 levels appear highly regulated by other components of the renin-angiotensin system, confirming its involvement in this system. Moreover, ACE2 expression in brain structures involved in the control of cardiovascular function suggests that the carboxypeptidase may have a role in the central regulation of blood pressure and diseases involving the autonomic nervous system, such as hypertension.

scholarly journals Regulation of brain renin-angiotensin system by benzamil-blockable sodium channels

1999 ◽  
Vol 276 (5) ◽  
pp. R1416-R1424 ◽  
Author(s):  
Masato Nishimura ◽  
Ken Ohtsuka ◽  
Naoharu Iwai ◽  
Hakuo Takahashi ◽  
Manabu Yoshimura
Keyword(s):  
Sodium Channels ◽  
Renin Angiotensin System ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Intracerebroventricular Infusion ◽  
Pcr Method ◽  
The Brain ◽  
Renal Hypertensive Rats

Changes in the renin-angiotensin system (RAS) mRNAs in the brain and the kidney of rats after administration of DOCA and/or sodium chloride were assessed by use of a competitive PCR method. Benzamil, a blocker of amiloride-sensitive sodium channels, was infused intracerebroventricularly or intravenously for 7 days in DOCA-salt or renal hypertensive rats, and the effects of benzamil on the brain RAS mRNAs were determined. Renin and ANG I-converting enzyme (ACE) mRNAs were not downregulated in the brain of rats administered DOCA and/or salt; however, these mRNAs were decreased in the kidney. Intracerebroventricular infusion of benzamil decreased renin, ACE, and ANG II type 1 receptor mRNAs in the brain of DOCA-salt hypertensive rats but not in the brain of renal hypertensive rats. The gene expression of the brain RAS, particularly renin and ACE, is regulated differently between the brain and the kidney in DOCA-salt hypertensive rats, and benzamil-blockable brain sodium channels may participate in the regulation of the brain RAS mRNAs.

scholarly journals Sympathoexcitation Associated with Renin-Angiotensin System in Metabolic Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Takuya Kishi ◽  
Yoshitaka Hirooka
Keyword(s):  
Metabolic Syndrome ◽  
Animal Studies ◽  
Renin Angiotensin System ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Activation ◽  
Sympathetic Nervous ◽  
The Brain

Renin-angiotensin system (RAS) is activated in metabolic syndrome (MetS), and RAS inhibitors are preferred for the treatments of hypertension with MetS. Although RAS activation is important for the therapeutic target, underlying sympathetic nervous system (SNS) activation is critically involved and should not be neglected in the pathogenesis of hypertension with MetS. In fact, previous studies have suggested that SNS activation has the interaction with RAS activation and/or insulin resistance. As a novel aspect connecting the importance of SNS and RAS activation, we and other investigators have recently demonstrated that angiotensin II type 1 receptor (AT1R) blockers (ARBs) improve SNS activation in patients with MetS. In the animal studies, SNS activation is regulated by the AT1R-induced oxidative stress in the brain. We have also demonstrated that orally administered ARBs cause sympathoinhibition independent of the depressor effects in dietary-induced hypertensive rats. Interestingly, these benefits on SNS activation of ARBs in clinical and animal studies are not class effects of ARBs. In conclusion, SNS activation associated with RAS activation in the brain should be the target of the treatment, and ARBs could have the potential benefit on SNS activation in patients with MetS.

scholarly journals Activation of the renin-angiotensin system, specifically in the subfornical organ is sufficient to induce fluid intake

2014 ◽  
Vol 307 (4) ◽  
pp. R376-R386 ◽  
Author(s):  
Jeffrey P. Coble ◽  
Martin D. Cassell ◽  
Deborah R. Davis ◽  
Justin L. Grobe ◽  
Curt D. Sigmund
Keyword(s):  
Fluid Intake ◽  
Resting Metabolic Rate ◽  
Renin Angiotensin System ◽  
Subfornical Organ ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Increased Activity ◽  
The Brain

Increased activity of the renin-angiotensin system within the brain elevates fluid intake, blood pressure, and resting metabolic rate. Renin and angiotensinogen are coexpressed within the same cells of the subfornical organ, and the production and action of ANG II through the ANG II type 1 receptor in the subfornical organ (SFO) are necessary for fluid intake due to increased activity of the brain renin-angiotensin system. We generated an inducible model of ANG II production by breeding transgenic mice expressing human renin in neurons controlled by the synapsin promoter with transgenic mice containing a Cre-recombinase-inducible human angiotensinogen construct. Adenoviral delivery of Cre-recombinase causes SFO-selective induction of human angiotensinogen expression. Selective production of ANG II in the SFO results in increased water intake but did not change blood pressure or resting metabolic rate. The increase in water intake was ANG II type 1 receptor-dependent. When given a choice between water and 0.15 M NaCl, these mice increased total fluid and sodium, but not water, because of an increased preference for NaCl. When provided a choice between water and 0.3 M NaCl, the mice exhibited increased fluid, water, and sodium intake, but no change in preference for NaCl. The increase in fluid intake was blocked by an inhibitor of PKC, but not ERK, and was correlated with increased phosphorylated cyclic AMP response element binding protein in the subfornical organ. Thus, increased production and action of ANG II specifically in the subfornical organ are sufficient on their own to mediate an increase in drinking through PKC.

UPREGULATION OF RENIN ANGIOTENSIN SYSTEM IN TYPE 1 DIABETES MELLITUS ASSOCIATED WITH HYPERTENSION

2011 ◽  
Vol 29 ◽  
pp. e377-e378
Author(s):  
L. Morais ◽  
I. Watanabe ◽  
M. Franco ◽  
D. Arita ◽  
M. Gabbay ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Divergent mechanism regulating fluid intake and metabolism by the brain renin-angiotensin system

2012 ◽  
Vol 302 (3) ◽  
pp. R313-R320 ◽  
Author(s):  
Curt D. Sigmund
Keyword(s):  
Blood Pressure ◽  
Fluid Intake ◽  
Renin Angiotensin System ◽  
Metabolic Effects ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Intracellular Form ◽  
Efferent Pathways ◽  
The Brain ◽  
Pituitary Adrenal Axis

The purpose of this review is two-fold. First, I will highlight recent advances in our understanding of the mechanisms regulating angiotensin II (ANG II) synthesis in the brain, focusing on evidence that renin is expressed in the brain and is expressed in two forms: a secreted form, which may catalyze extracellular ANG I generation from glial or neuronal angiotensinogen (AGT), and an intracellular form, which may generate intracellular ANG in neurons that may act as a neurotransmitter. Second, I will discuss recent studies that advance the concept that the renin-angiotensin system (RAS) in the brain not only is a potent regulator of blood pressure and fluid intake but may also regulate metabolism. The efferent pathways regulating the blood pressure/dipsogenic effects and the metabolic effects of elevated central RAS activity appear different, with the former being dependent upon the hypothalamic-pituitary-adrenal axis, and the latter being dependent upon an interaction between the brain and the systemic (or adipose) RAS.

The Brain-Renin-Angiotensin System: Update

1986 ◽  
pp. 123-133 ◽  
Author(s):  
Thomas Unger ◽  
Detlev Ganten ◽  
Gerald Ludwig ◽  
Rudolf E. Lang
Keyword(s):  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Brain
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