Brain Angiotensin II, an Important Stress Hormone: Regulatory Sites and Therapeutic Opportunities

Saavedra, Juan M.; Ando, Hiromichi; Armando, Inés; Baiardi, Gustavo; Bregonzio, Claudia; Ježová, M; Zhou, Jin

doi:10.1196/annals.1296.009

Cited by 72 publications

(44 citation statements)

References 25 publications

(35 reference statements)

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“…5,6 In particular, it has been shown that central or systemic administration of AT 1 receptor antagonists attenuated the increase in blood pressure and plasma catecholamine levels caused by several psycho-and physico-emotional stressors in rats and rabbits. 12,[24][25][26] Our data extend these findings by showing that targeted deletion of the AT 1A receptor gene selectively attenuates the pressor response to stress in mice.…”

Section: Stress Responsementioning

confidence: 99%

“…Recent pharmacological studies, however, indicate that the activation of angiotensin II type 1 (AT 1 ) receptors, and specifically those in the dorsomedial hypothalamus (DMH) and rostral ventrolateral medulla (RVLM), is required for full expression of sympathetic cardiovascular responses to various psychoemotional stressors in rats and rabbits. [3][4][5][6][7] Nonetheless, the effect of genetic deficiency of AT 1 receptors on cardiovascular reactivity to stress is yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Blood pressure reactivity to emotional stress is reduced in AT1A-receptor knockout mice on normal, but not high salt intake

et al. 2009

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Pharmacological evidence suggests that angiotenisn II type 1 (AT 1 ) receptors are involved in the regulation of cardiovascular response to emotional stress and reinforcing effect of dietary salt on this response. In this study, we examined the effect of genetic deletion of AT 1A receptors on the cardiovascular effects of stress and salt in mice. AT 1A receptor knockout (AT 1A À/À ) and wild-type (AT 1A +/+ ) mice were implanted with telemetry devices and placed on a normal (0.4%) or high (3.1%) salt diet (HSD). Resting blood pressure (BP) in AT 1AÀ/À mice (84 ± 3 mm Hg) was lower than in AT 1A +/+ mice (107 ± 2 mm Hg). Negative emotional (restraint) stress increased BP by 33±3 mm Hg in AT 1A +/+ mice. This response was attenuated by 40% in AT 1AÀ/À mice (18 ± 3 mm Hg). Conversely, the BP increase caused by food presentation and feeding was similar in AT 1AÀ/À (25 ± 3 mm Hg) and AT 1A +/+ mice (26 ± 3 mm Hg). HSD increased resting BP by 14 ± 4 mm Hg in AT 1A À/À mice without affecting it significantly in AT 1A +/+ mice. Under these conditions, the pressor response to restraint stress in AT 1A À/À mice (30±3 mm Hg) was no longer different from that in wild-type animals (28 ± 3 mm Hg). The BP response to feeding was not altered by HSD in either AT 1A À/À or AT 1A +/+ mice (25 ± 2 and 27 ± 3 mm Hg, respectively). These results indicate that AT 1A receptor deficiency leads to a reduction in BP reactivity to negative emotional stress, but not feeding. HSD can selectively reinforce the cardiovascular response to negative stress in AT 1A À/À mice. However, there is little interaction between AT 1A receptors, excess dietary sodium and feeding-induced cardiovascular arousal.

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Section: Stress Responsementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Blood pressure reactivity to emotional stress is reduced in AT1A-receptor knockout mice on normal, but not high salt intake

et al. 2009

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“…ANG II signaling in the PVN plays an important role in mediating both the HPA axis and autonomic responses to stress (4,6,9,11,51). Moreover, PVN AT 1 R expression is increased in SHRs and in normotensive rats following repeated restraint and 24-h isolation stress (51), and systemic administration of an AT 1 R antagonist blunts the sympathoadrenal response to stress in SHRs (25).…”

Section: Discussionmentioning

confidence: 99%

“…The paraventricular nucleus of the hypothalamus (PVN) plays a central role in integrating the physiological response to stress, and angiotensin II (ANG II) signaling within the PVN has been shown to contribute to both the activation of the hypothalamic-pituitary-adrenal (HPA) axis and elevations in blood pressure and heart rate during stress (1,6,14,31,51). Previous work from our laboratory demonstrated that within the brain macrophage migration inhibitory factor (MIF) is an important intracellular counterregulator of ANG II in PVN neurons and that this action is mediated by the intrinsic thiol-protein oxidoreductase (TPOR) activity that is exerted by a C-A-L-C motif at residues 57-60 of MIF (40,57,58).…”

Section: Exaggerated Activation Of the Sympathetic Nervous System Andmentioning

confidence: 99%

“…Stress also activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated plasma glucocorticoid concentrations (cortisol in humans, corticosterone in rats), and elevated glucocorticoids confer additional risk for hypertension and related cardiovascular disease (49, 61,62). Despite the important influence stress-induced increases in blood pressure and HPA axis activity have on cardiovascular health, the central mechanisms influencing the magnitude of these responses are incompletely understood.The paraventricular nucleus of the hypothalamus (PVN) plays a central role in integrating the physiological response to stress, and angiotensin II (ANG II) signaling within the PVN has been shown to contribute to both the activation of the hypothalamic-pituitary-adrenal (HPA) axis and elevations in blood pressure and heart rate during stress (1,6,14,31,51). Previous work from our laboratory demonstrated that within the brain macrophage migration inhibitory factor (MIF) is an important intracellular counterregulator of ANG II in PVN neurons and that this action is mediated by the intrinsic thiol-protein oxidoreductase (TPOR) activity that is exerted by a C-A-L-C motif at residues 57-60 of MIF (40,57,58).…”

mentioning

confidence: 99%

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Novel mechanism within the paraventricular nucleus reduces both blood pressure and hypothalamic pituitary-adrenal axis responses to acute stress

Erdös

Clifton

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Erdos B, Clifton RR, Liu M, Li H, McCowan ML, Sumners C, Scheuer DA. Novel mechanism within the paraventricular nucleus reduces both blood pressure and hypothalamic pituitary-adrenal axis responses to acute stress. Am J Physiol Heart Circ Physiol 309: H634-H645, 2015. First published June 12, 2015 doi:10.1152/ajpheart.00207.2015.-Macrophage migration inhibitory factor (MIF) counteracts pressor effects of angiotensin II (ANG II) in the paraventricular nucleus of the hypothalamus (PVN) in normotensive rats, but this mechanism is absent in spontaneously hypertensive rats (SHRs) due to a lack of MIF in PVN neurons. Since endogenous ANG II in the PVN modulates stress reactivity, we tested the hypothesis that replacement of MIF in PVN neurons would reduce baseline blood pressure and inhibit stressinduced increases in blood pressure and plasma corticosterone in adult male SHRs. Radiotelemetry transmitters were implanted to measure blood pressure, and then an adeno-associated viral vector expressing either enhanced green fluorescent protein (GFP) or MIF was injected bilaterally into the PVN. Cardiovascular responses to a 15-min water stress (1-cm deep, 25°C) and a 60-min restraint stress were evaluated 3-4 wk later. MIF treatment in the PVN attenuated average restraintinduced increases in blood pressure (37.4 Ϯ 2.0 and 27.6 Ϯ 3.5 mmHg in GFP and MIF groups, respectively, P Ͻ 0.05) and corticosterone (42 Ϯ 2 and 36 Ϯ 3 g/dl in GFP and MIF groups, respectively, P Ͻ 0.05). MIF treatment in the PVN also reduced stress-induced elevations in the number of c-Fos-positive cells in the rostral ventrolateral medulla (71 Ϯ 5 in GFP and 47 Ϯ 5 in MIF SHRs, P Ͻ 0.01) and corticotropin-releasing factor mRNA expression in the PVN. However, MIF had no significant effects on the cardiovascular responses to water stress in SHRs or to either stress in Sprague-Dawley rats. Therefore, viral vector-mediated restoration of MIF in PVN neurons of SHRs attenuates blood pressure and hypothalamic pituitary adrenal axis responses to stress. psychological stress; blood pressure; brain; angiotensin ii; hypertension NEW & NOTEWORTHY Exaggerated activation of the sympathetic nervous system and/or the hypothalamic-pituitary-adrenal (HPA) axis increases cardiovascular disease risk. The present study demonstrates that macrophage migration inhibitory factor (MIF) in paraventricular nucleus (PVN) neurons is a novel mechanism mediating attenuation of both the sympathetic and HPA axis responses to acute stress.SEVERAL LINES OF EVIDENCE suggest that the amplitude of blood pressure increases in response to psychological or physical stressors in young and middle-aged normotensive adults elevates the risk of developing hypertension and other cardiovascular diseases such as coronary artery disease, myocardial ischemia, and stroke later in their life (8,20,39,41,42,44,50,60). Larger variations in blood pressure in response to repeated everyday stressors may lead to accelerated damage of the kidneys and vasculature. Altered central mechanisms that mediate augmented...

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Endocannabinoid system in the adult rat circumventricular areas: An immunohistochemical study

Suárez¹,

Romero-Zerbo²,

Rivera³

et al. 2010

J of Comparative Neurology

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Endocannabinoids (ECs) are important neuromodulators involved in a plethora of physiological processes such as modulation of synaptic transmission, neuroprotection, immune function, and neurodevelopment, among others. However, still lacking is a detailed study on the presence of this system in the circumventricular areas, brain structures controlling the interaction between cerebrospinal fluid and brain parenchyma. The aim of this work was to provide the anatomical basis supporting a functional role of ECs in the activity of circumventricular areas. To this end, an immunohistochemical study of the EC system in rat brain was performed. Receptors and synthesizing and degrading enzymes for ECs were widely distributed in rat ependyma and subependyma, marginal glia, and circumventricular organs (CVOs) such as the choroid plexus, subfornical organ, subcommissural organ, median eminence, and area postrema. These zones constitute barrier systems between the brain parenchyma and the ventricular or subarachnoid cerebrospinal fluid (CSF) and between the extracellular hemal milieu of CVOs and the brain parenchyma or the CSF. By immunohistochemistry and real-time polymerase chain reaction we found DAGLalpha, DAGLbeta, NAPE-PLD, MAGL, and FAAH in the ependyma. These finding suggest that the ependyma can release and clear ECs from the ventricular CSF. Subependymal astrocytes and tanycytes displayed DAGLalpha immunoreactivity but parenchymal astrocytes did not express EC-synthesizing enzymes, thus establishing a sharp distinction between these two astrocyte populations. CB1 was located in fibers innervating discrete subventricular zones such as the neurogenic striatal subventricular zone and the fourth ventricle. CB1 fibers also innervated some CVOs.

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Brain Angiotensin II, an Important Stress Hormone: Regulatory Sites and Therapeutic Opportunities

Cited by 72 publications

References 25 publications

Blood pressure reactivity to emotional stress is reduced in AT1A-receptor knockout mice on normal, but not high salt intake

Blood pressure reactivity to emotional stress is reduced in AT1A-receptor knockout mice on normal, but not high salt intake

Novel mechanism within the paraventricular nucleus reduces both blood pressure and hypothalamic pituitary-adrenal axis responses to acute stress

Endocannabinoid system in the adult rat circumventricular areas: An immunohistochemical study

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