Role of area postrema pressor mechanisms in the regulation of arterial pressure

1987 ◽  
Vol 65 (8) ◽  
pp. 1591-1597 ◽  
Author(s):  
Carlos M. Ferrario ◽  
Karen L. Barnes ◽  
Debra I. Diz ◽  
Christine H. Block ◽  
David B. Averill
Keyword(s):  
Angiotensin Ii ◽  
Binding Sites ◽  
Area Postrema ◽  
Intrinsic Activity ◽  
Motor Nucleus ◽  
Additional Information ◽  
The Central Nervous System ◽  
Nuclear Regions

This article discusses the data which established that angiotensin II modulates the tonic and reflex control of cardiovascular function by actions on the nuclear regions of the dorsal medulla oblongata. Although physiological evidence for the modulatory actions of angiotensin II in structures of the lower brainstem has been gathered over the past 16 years, only the recent application of new neurobiological techniques has allowed a more definitive understanding of its role. The identification of high affinity angiotensin II binding sites within the parenchyma of the area postrema with the technique of in vitro receptor autoradiography has provided anatomical validity for a role of angiotensin II in the central nervous system. The added discovery of angiotensin II binding sites in subnuclear components of the nucleus tractus solitarii and the motor nucleus of the tenth cranial nerve provides additional information on the various mechanisms through which angiotensin II may affect the intrinsic activity of the brainstem neuronal circuits involved in the integration of baroreceptor and sensory visceromotor function.

scholarly journals LPS Primes Brain Responsiveness to High Mobility Group Box-1 Protein

2021 ◽  
Vol 14 (6) ◽  
pp. 558
Author(s):  
Verena Peek ◽  
Lois M. Harden ◽  
Jelena Damm ◽  
Ferial Aslani ◽  
Stephan Leisengang ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Area Postrema ◽  
High Mobility ◽  
High Mobility Group ◽  
Direct Access ◽  
Significant Release ◽  
Factor Α ◽  
Culture Supernatants

High mobility group box (HMGB)1 action contributes to late phases of sepsis, but the effects of increased endogenous plasma HMGB1 levels on brain cells during inflammation are unclear. Here, we aimed to further investigate the role of HMGB1 in the brain during septic-like lipopolysaccharide-induced inflammation in rats (LPS, 10 mg/kg, i.p.). HMGB-1 mRNA expression and release were measured in the periphery/brain by RT-PCR, immunohistochemistry and ELISA. In vitro experiments with disulfide-HMGB1 in primary neuro-glial cell cultures of the area postrema (AP), a circumventricular organ with a leaky blood–brain barrier and direct access to circulating mediators like HMGB1 and LPS, were performed to determine the direct influence of HMGB1 on this pivotal brain structure for immune-to-brain communication. Indeed, HMGB1 plasma levels stayed elevated after LPS injection. Immunohistochemistry of brains and AP cultures confirmed LPS-stimulated cytoplasmatic translocation of HMGB1 indicative of local HMGB1 release. Moreover, disulfide-HMGB1 stimulation induced nuclear factor (NF)-κB activation and a significant release of interleukin-6, but not tumor necrosis factor α, into AP culture supernatants. However, only a few AP cells directly responded to HMGB1 with increased intracellular calcium concentration. Interestingly, priming with LPS induced a seven-fold higher percentage of responsive cells to HMGB1. We conclude that, as a humoral and local mediator, HMGB1 enhances brain inflammatory responses, after LPS priming, linked to sustained sepsis symptoms.

Temperature-dependence of the DnaA–DNA interaction and its effect on the autoregulation of dnaA expression

2012 ◽  
Vol 449 (2) ◽  
pp. 333-341 ◽  
Author(s):  
Chiara Saggioro ◽  
Anne Olliver ◽  
Bianca Sclavi
Keyword(s):  
Temperature Dependence ◽  
Binding Sites ◽  
Dna Interaction ◽  
Bacterial Dna ◽  
Dnaa Protein ◽  
High Affinity ◽  
Key Factor

The DnaA protein is a key factor for the regulation of the timing and synchrony of initiation of bacterial DNA replication. The transcription of the dnaA gene in Escherichia coli is regulated by two promoters, dnaAP1 and dnaAP2. The region between these two promoters contains several DnaA-binding sites that have been shown to play an important role in the negative auto-regulation of dnaA expression. The results obtained in the present study using an in vitro and in vivo quantitative analysis of the effect of mutations to the high-affinity DnaA sites reveal an additional effect of positive autoregulation. We investigated the role of transcription autoregulation in the change of dnaA expression as a function of temperature. While negative auto-regulation is lost at dnaAP1, the effects of both positive and negative autoregulation are maintained at the dnaAP2 promoter upon lowering the growth temperature. These observations can be explained by the results obtained in vitro showing a difference in the temperature-dependence of DnaA–ATP binding to its high- and low-affinity sites, resulting in a decrease in DnaA–ATP oligomerization at lower temperatures. The results of the present study underline the importance of the role for autoregulation of gene expression in the cellular adaptation to different growth temperatures.

Losartan Increases No Production from the Bovine Aortic Wall That is Stimulated by Angiotensin II

2003 ◽  
Vol 1 (3) ◽  
pp. 113-117 ◽  
Author(s):  
M. Myronidou ◽  
B. Kokkas ◽  
A. Kouyoumtzis ◽  
N. Gregoriadis ◽  
A. Lourbopoulos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Aortic Wall ◽  
Vascular Wall ◽  
Protective Role ◽  
Normal Function ◽  
No Production ◽  
Chemical Inactivation

In these studies we investigated if losartan, an AT1- receptor blocker has any beneficial effect on NO production from the bovine aortic preparations in vitro while under stimulation from angiotensin II. Experiments were performed on intact specimens of bovine thoracic aorta, incubated in Dulbeco's MOD medium in a metabolic shaker for 24 hours under 95 % O2 and 5 % CO2 at a temperature of 37°C. We found that angiotensin II 1nM−10 μM does not exert any statistically significant action on NO production. On the contrary, angiotensin II 10nM increases the production of NO by 58.14 % (from 12.16 + 2.9 μm/l to 19.23 + 4.2 μm/l in the presence of losartan 1nM (P<0.05). Nitric oxide levels depend on both rate production and rate catabolism or chemical inactivation. Such an equilibrium is vital for the normal function of many systems including the cardiovascular one. The above results demonstrate that the blockade of AT1-receptors favors the biosynthesis of NO and indicate the protective role of losartan on the vascular wall.

scholarly journals The role of Neuropilin-1 in COVID-19

2021 ◽  
Vol 17 (1) ◽  
pp. e1009153
Author(s):  
Bindu S. Mayi ◽  
Jillian A. Leibowitz ◽  
Arden T. Woods ◽  
Katherine A. Ammon ◽  
Alphonse E. Liu ◽  
...  
Keyword(s):  
Immune Function ◽  
Viral Entry ◽  
Axonal Guidance ◽  
Cell Surface Receptor ◽  
Neuropilin 1 ◽  
Surface Receptor ◽  
The Central Nervous System

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae.

Advances in microglia cellular models: focus on extracellular vesicle production

2021 ◽  
Author(s):  
Lorenzo Ceccarelli ◽  
Laura Marchetti ◽  
Chiara Giacomelli ◽  
Claudia Martini
Keyword(s):  
Cell Communication ◽  
Extracellular Vesicle ◽  
Cellular Models ◽  
Advantages And Disadvantages ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Harmful Effects ◽  
Brain Homeostasis

Microglia are the major component of the innate immune system in the central nervous system. They promote the maintenance of brain homeostasis as well as support inflammatory processes that are often related to pathological conditions such as neurodegenerative diseases. Depending on the stimulus received, microglia cells dynamically change their phenotype releasing specific soluble factors and largely modify the cargo of their secreted extracellular vesicles (EVs). Despite the mechanisms at the basis of microglia actions have not been completely clarified, the recognized functions exerted by their EVs in patho-physiological conditions represent the proof of the crucial role of these organelles in tuning cell-to-cell communication, promoting either protective or harmful effects. Consistently, in vitro cell models to better elucidate microglia EV production and mechanisms of their release have been increased in the last years. In this review, the main microglial cellular models that have been developed and validated will be described and discussed, with particular focus on those used to produce and derive EVs. The advantages and disadvantages of their use will be evidenced too. Finally, given the wide interest in applying EVs in diagnosis and therapy too, the heterogeneity of available models for producing microglia EVs is here underlined, to prompt a cross-check or comparison among them.

scholarly journals Intranasal Borna Disease Virus (BoDV-1) Infection: Insights into Initial Steps and Potential Contagiosity

2019 ◽  
Vol 20 (6) ◽  
pp. 1318 ◽  
Author(s):  
Alexandra Kupke ◽  
Sabrina Becker ◽  
Konstantin Wewetzer ◽  
Barbara Ahlemeyer ◽  
Markus Eickmann ◽  
...  
Keyword(s):  
Viral Infections ◽  
Cell Types ◽  
Nerve Fibers ◽  
Olfactory Pathway ◽  
Adult Rats ◽  
The Central Nervous System ◽  
Receptor Neurons

Mammalian Bornavirus (BoDV-1) typically causes a fatal neurologic disorder in horses and sheep, and was recently shown to cause fatal encephalitis in humans with and without transplant reception. It has been suggested that BoDV-1 enters the central nervous system (CNS) via the olfactory pathway. However, (I) susceptible cell types that replicate the virus for successful spread, and (II) the role of olfactory ensheathing cells (OECs), remained unclear. To address this, we studied the intranasal infection of adult rats with BoDV-1 in vivo and in vitro, using olfactory mucosal (OM) cell cultures and the cultures of purified OECs. Strikingly, in vitro and in vivo, viral antigen and mRNA were present from four days post infection (dpi) onwards in the olfactory receptor neurons (ORNs), but also in all other cell types of the OM, and constantly in the OECs. In contrast, in vivo, BoDV-1 genomic RNA was only detectable in adult and juvenile ORNs, nerve fibers, and in OECs from 7 dpi on. In vitro, the rate of infection of OECs was significantly higher than that of the OM cells, pointing to a crucial role of OECs for infection via the olfactory pathway. Thus, this study provides important insights into the transmission of neurotropic viral infections with a zoonotic potential.

scholarly journals Angiotensin II infusion in vivo does not modulate cortisol secretion in the late-gestation ovine fetus

1998 ◽  
Vol 275 (2) ◽  
pp. R357-R362 ◽  
Author(s):  
Kirsten R. Poore ◽  
I. Ross Young ◽  
Benedict J. Canny ◽  
Geoffrey D. Thorburn
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Gland ◽  
Late Gestation ◽  
Treatment Groups ◽  
Arterial Blood ◽  
Basal Cortisol ◽  
Ovine Fetus

Maturation of the fetal adrenal gland is critical for the onset of ovine parturition. It has long been proposed that the fetal adrenal gland may be under inhibitory influences during late gestation. In vitro evidence has suggested that angiotensin II may be such an inhibitory factor and may help to prevent a premature increase in cortisol concentrations. The aim of this study was to test the effect of angiotensin II infusion in vivo on basal cortisol concentrations and fetal adrenal responsiveness to an ACTH-(1—24) challenge. Fetuses received a continuous infusion of either angiotensin II (100 ng ⋅ min−1 ⋅ kg−1; n = 7) or saline (2 ml/h; n = 4), which commenced at 140 days of gestation (GA) and continued for a total of 50 h. Adrenal responsiveness to the administration of ACTH-(1—24) (5 μg/kg) was determined during angiotensin II or saline infusions at both 2 and 48 h after infusion onset. Angiotensin II had no significant effect on adrenal responsiveness after acute (2 h) or chronic (48 h) infusion. There was no effect of saline or angiotensin II infusion on basal immunoreactive ACTH or cortisol concentrations after 2 h, but there was a significant increase in basal cortisol concentrations in both treatment groups by 48 h, probably reflecting the normal rise in cortisol concentrations at this GA. Mean arterial blood pressure was significantly increased in angiotensin II-infused fetuses only. This study has therefore found no evidence to suggest that angiotensin II infusion in vivo modulates fetal basal cortisol concentrations or adrenal responsiveness in the last week of gestation, in contrast with previous in vitro studies. These results throw into question the proposed role of angiotensin II as a negative modulator of adrenal function in the ovine fetus.

scholarly journals Analysis of the structural requirements of sugar binding to the liver, brain and insulin-responsive glucose transporters expressed in oocytes

1993 ◽  
Vol 294 (3) ◽  
pp. 753-760 ◽  
Author(s):  
C A Colville ◽  
M J Seatter ◽  
G W Gould
Keyword(s):  
Hydrogen Bond ◽  
Binding Sites ◽  
Glucose Transporters ◽  
Binding Pocket ◽  
Structural Basis ◽  
Sugar Binding ◽  
Glucose Analogues ◽  
Sugar Recognition

We have expressed the liver (GLUT 2), brain (GLUT 3) and insulin-responsive (GLUT 4) glucose transporters in oocytes from Xenopus laevis by microinjection of in vitro-transcribed mRNA. Using a range of halogeno- and deoxy-glucose analogues, and other hexoses, we have studied the structural basis of sugar binding to these different isoforms. We show that a hydrogen bond to the C-3 position is involved in sugar binding for all three isoforms, but that the direction of this hydrogen bond is different in GLUT 2 from either GLUT 1, 3 or 4. Hydrogen-bonding at the C-4 position is also involved in sugar recognition by all three isoforms, but we propose that in GLUT 3 this hydrogen bond plays a less significant role than in GLUT 2 and 4. In all transporters we propose that the C-4 position is directed out of the sugar-binding pocket. The role of the C-6 position is also discussed. In addition, we have analysed the ability of fructopyranose and fructofuranose analogues to inhibit the transport mediated by GLUT2. We show that fructofuranose analogues, but not fructopyranose analogues, are efficient inhibitors of transport mediated by GLUT 2, and therefore suggest that GLUT 2 accommodates D-glucose as a pyranose ring, but D-fructose as a furanose ring. Models for the binding sites of GLUT 2, 3 and 4 are presented.

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