Joint effect of mid- and late-life blood pressure on the brain: The AGES-Reykjavik Study

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

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Is High Blood Pressure Self-Protection for the Brain?

Circulation Research ◽

10.1161/circresaha.116.309493 ◽

2016 ◽

Vol 119 (12) ◽

Cited By ~ 37

Author(s):

Esther A.H. Warnert ◽

Jonathan C.L. Rodrigues ◽

Amy E. Burchell ◽

Sandra Neumann ◽

Laura E.K. Ratcliffe ◽

...

Keyword(s):

Blood Pressure ◽

High Blood Pressure ◽

Self Protection ◽

The Brain

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O1-03-02: Blood pressure, memory, and executive function changes in late-life

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.215 ◽

2012 ◽

Vol 8 (4S_Part_3) ◽

pp. P88-P88 ◽

Cited By ~ 1

Author(s):

Shahram Oveisgharan ◽

Alina Solomon ◽

Miia Kivipelto ◽

Vladimir Hachinski

Keyword(s):

Blood Pressure ◽

Executive Function ◽

Late Life

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00575.2011 ◽

2012 ◽

Vol 302 (3) ◽

pp. R313-R320 ◽

Cited By ~ 15

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.

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Control of Blood Pressure and the Distribution of Blood Flow

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462300012551 ◽

1991 ◽

Vol 7 (S1) ◽

pp. 79-84 ◽

Cited By ~ 1

Author(s):

Hans T. Versmold

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Cardiac Output ◽

Peripheral Resistance ◽

Systemic Blood Pressure ◽

Adrenergic Innervation ◽

Systemic Blood ◽

Low Cardiac Output ◽

Neurohumoral Control ◽

The Brain

Systemic blood pressure (BP) is the product of cardiac output and total peripheral resistance. Cardiac output is controlled by the heart rate, myocardial contractility, preload, and afterload. Vascular resistance (vascular hindrance × viscosity) is under local autoregulation and general neurohumoral control through sympathetic adrenergic innervation and circulating catecholamines. Sympathetic innovation predominates in organs receivingflowin excess of their metabolic demands (skin, splanchnic organs, kidney), while innervation is poor and autoregulation predominates in the brain and heart. The distribution of blood flow depends on the relative resistances of the organ circulations. During stress (hypoxia, low cardiac output), a raise in adrenergic tone and in circulating catecholamines leads to preferential vasoconstriction in highly innervated organs, so that blood flow is directed to the brain and heart. Catecholamines also control the levels of the vasoconstrictors renin, angiotensin II, and vasopressin. These general principles also apply to the neonate.

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