Colocalization of angiotensinogen and glial fibrillary acidic protein in astrocytes in rat brain

Deschepper, Christian F.; Bouhnik, J; Ganong, William F.

doi:10.1016/0006-8993(86)90411-7

Cited by 127 publications

(59 citation statements)

References 13 publications

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“…Strong TEER and better barrier properties can be reinduced when cells are grown in the presence of ACM (Arthur et al, 1987;Neuhaus et al, 1991;Abbott, 2002). Our data support previous reports showing AGT expression by rodent astrocytes (Clemens et al, 1986;Deschepper et al, 1986;Lynch et al, 1987;Stornetta et al, 1988) and demonstrate AT 1 and AT 2 receptor expression by human microvascular brain ECs in situ. Our study provides evidence that astrocyte-produced AngII, acting on human BBB-ECs via the AT 1 receptor, is an important effector of astrocytic reinduction of BBB integrity in vitro, a situation analogous to vascular repair of the BBB after injury.…”

Section: Discussionsupporting

confidence: 81%

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Cayrol²,

et al. 2007

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The blood-brain barrier (BBB) restricts molecular and cellular trafficking between the blood and the CNS. Although astrocytes are known to control BBB permeability, the molecular determinants of this effect remain unknown. We show that angiotensinogen (AGT) produced and secreted by astrocytes is cleaved into angiotensin II (AngII) and acts on type 1 angiotensin receptors (AT 1 ) expressed by BBB endothelial cells (ECs). Activation of AT 1 restricts the passage of molecular tracers across human BBB-derived ECs through threonine-phosphorylation of the tight junction protein occludin and its mobilization to lipid raft membrane microdomains. We also show that AGT knock-out animals have disorganized occludin strands at the level of the BBB and a diffuse accumulation of the endogenous serum protein plasminogen in the CNS, compared with wild-type animals. Finally, we demonstrate a reduction in the number of AGT-immunopositive perivascular astrocytes in multiple sclerosis (MS) lesions, which correlates with a reduced expression of occludin similarly seen in the CNS of AGT knock-out animals. Such a reduction in astrocyte-expressed AGT and AngII is dependent, in vitro, on the proinflammatory cytokines tumor necrosis factor-␣ and interferon-␥. Our study defines a novel physiological role for AngII in the CNS and suggests that inflammation-induced downregulation of AngII production by astrocytes is involved in BBB dysfunction in MS lesions.

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Section: Discussionsupporting

confidence: 81%

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Cayrol²,

et al. 2007

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“…Both methods show that AGT is widely expressed in astrocytes (32,131), and in those cells, was localized in the nucleus (122). Genetic deletion of glial-specific AGT lowers arterial pressure in double transgenic mice expressing both human renin and human AGT (121), and antisense inhibition of glial AGT in rats results is altered baroreflex regulation and increased exercise tolerance (43,119).…”

Section: Localization Of Ras Components Required For Ang II Productionmentioning

confidence: 99%

Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

Coble¹,

Grobe

Johnson³

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Coble JP, Grobe JL, Johnson AK, Sigmund CD. Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ. Am J Physiol Regul Integr Comp Physiol 308: R238 -R249, 2015. First published December 17, 2014 doi:10.1152/ajpregu.00486.2014.-It is critical for cells to maintain a homeostatic balance of water and electrolytes because disturbances can disrupt cellular function, which can lead to profound effects on the physiology of an organism. Dehydration can be classified as either intra-or extracellular, and different mechanisms have developed to restore homeostasis in response to each. Whereas the renin-angiotensin system (RAS) is important for restoring homeostasis after dehydration, the pathways mediating the responses to intra-and extracellular dehydration may differ. Thirst responses mediated through the angiotensin type 1 receptor (AT 1R) and angiotensin type 2 receptors (AT 2R) respond to extracellular dehydration and intracellular dehydration, respectively. Intracellular signaling factors, such as protein kinase C (PKC), reactive oxygen species (ROS), and the mitogen-activated protein (MAP) kinase pathway, mediate the effects of central angiotensin II (ANG II). Experimental evidence also demonstrates the importance of the subfornical organ (SFO) in mediating some of the fluid intake effects of central ANG II. The purpose of this review is to highlight the importance of the SFO in mediating fluid intake responses to dehydration and ANG II.angiotensin; blood pressure; barin; fluid; renin FLUID BALANCE is crucial for the homeostasis and survival of organisms because they have to properly maintain fluid and electrolyte concentrations for the normal function of all cells. Fluid balance can go awry in pathological states such as in chronic kidney disease and diabetes. Among its many roles in maintaining homeostasis, the renin-angiotensin system (RAS) is an important regulator of fluid balance. The RAS achieves this through the actions of its main effector peptide, angiotensin II (ANG II) through the ANG II type 1 (AT 1 R) and type 2 (AT 2 R) receptors. Activation of AT 1 R by blood-borne ANG II in target tissues causes increases in sodium and water retention, arginine vasopressin (AVP), and aldosterone release, vasoconstriction, increased sympathetic nervous system activity, and increased fluid intake. ANG II is produced by the consecutive enzymatic action of renin on its substrate angiotensinogen (AGT) and by angiotensin-converting enzyme (ACE) on its substrate angiotensin I (ANG I). The renin-AGT cleavage step is generally the rate-limiting step in the production of ANG II, and this is certainly true in the brain where the amount of renin is limiting. The RAS exists in two forms: a circulatory form where ANG II acts as an endocrine factor, and a tissue-specific form, where local production of ANG II acts in an autocrine or paracrine manner to induce AT 1 R signaling on ANG II producing or nearby cells (75). Intracrine, or intracellular forms of the RAS, hav...

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“…In conscious ASrAOGEN rats, resting MAP is slightly lower and BRS is slightly higher than in SD rats (2,3,14,34,54,62). Although astrocytes may be the main source of angiotensinogen in the brain, it is also expressed in neurons, as supported by studies in which renin and angiotensinogen are synthesized by cells in culture and by intact brain (15,16,37,38,55,60). We recently found that ANG II and ANG-(1-7) immunoreactivity was similar in neuronal pathways in SD and ASrAOGEN rats (61), suggesting that the neuronal expression of the two peptides might be intact in the face of a depleted glial source of the peptides.…”

mentioning

confidence: 91%

Baroreceptor reflex regulation in anesthetized transgenic rats with low glia-derived angiotensinogen

Sakima¹,

Averill²,

Каспер³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Sakima A, Averill DB, Kasper SO, Jackson LR, Ganten D, Ferrario CM, Gallagher PE, Diz DI. Baroreceptor reflex regulation in anesthetized transgenic rats with low glia-derived angiotensinogen. Am J Physiol Heart Circ Physiol 292: H1412-H1419, 2007. First published November 3, 2006; doi:10.1152/ajpheart.00984.2006.-Endogenous angiotensin (ANG) II and ANG-(1-7) act at the nucleus tractus solitarius (NTS) to differentially modulate neural control of the circulation. The role of these peptides endogenous to NTS on cardiovascular reflex function was investigated in transgenic rats with low brain angiotensinogen (Aogen) due to glial overexpression of an antisense to Aogen (ASrAOGEN) and in Sprague-Dawley (SD) rats. Arterial baroreceptor reflex sensitivity (BRS) for control of heart rate (HR) in response to increases in mean arterial pressure (MAP) was tested before and after bilateral microinjection of the angiotensin type 1 (AT 1) receptor blocker candesartan or the ANG-(1-7) receptor blocker (D-Ala 7 )-ANG-(1-7) into the NTS of urethane-chloraloseanesthetized ASrAOGEN and SD rats. Baseline MAP was higher in ASrAOGEN than in SD rats under anesthesia (P Ͻ 0.01). Injection of candesartan or (D-Ala 7 )-ANG-(1-7) decreased MAP (P Ͻ 0.01) and HR (P Ͻ 0.05) in ASrAOGEN, but not SD, rats. The BRS at baseline was similar in ASrAOGEN and SD rats. Candesartan increased BRS by 41% in SD rats (P Ͻ 0.01) but was without effect in ASrAOGEN rats. In contrast, the reduction in BRS after (D-Ala 7 )-ANG-(1-7) administration was comparable in SD (31%) and ASrAOGEN rats (34%). These findings indicate that the absence of glia-derived Aogen is associated with 1) an increase in MAP under anesthesia mediated via AT 1 and ANG-(1-7) receptors within the NTS, 2) the absence of an endogenous ANG II contribution to tonic inhibition of BRS, and 3) a continued contribution of endogenous ANG-(1-7) to tonic enhancement of BRS.baroreceptors; solitary tract nucleus; brain renin-angiotensin system; transgenic rats ENDOGENOUS ANGIOTENSIN (ANG) II contributes to cardiovascular and autonomic reflex function (1,8,17,21,52). ANG II receptors have been identified in the nucleus tractus solitarius (NTS), where baroreceptor and chemoreceptor afferents terminate and ANG II, of endogenous or exogenous origin, is known to attenuate baroreflex function (1,8,11,14,24,30,40,46). ANG-(1-7) is also present in the brain, in the hypothalamus and medulla oblongata, at concentrations equivalent to or greater than ANG II (12). ANG-(1-7), from endogenous or exogenous sources, enhances baroreflex control of heart rate (HR), resulting in actions opposite to those of ANG II (1, 6, 9, 13, 21, 44, 52).Transgenic animals are useful for investigation of the functional role of the brain renin-angiotensin system (RAS) in cardiovascular regulation and fluid homeostasis. In fact, glial and neuronal overexpression of renin and angiotensinogen produces different patterns of alterations in resting arterial pressure and baroreceptor reflex function. Morimoto et al. (42,43) recently demonst...

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Colocalization of angiotensinogen and glial fibrillary acidic protein in astrocytes in rat brain

Cited by 127 publications

References 13 publications

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

Baroreceptor reflex regulation in anesthetized transgenic rats with low glia-derived angiotensinogen

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