scholarly journals PTSD as an Endothelial Disease: Insights From COVID-19

2021 ◽  
Vol 15 ◽  
Author(s):  
Adonis Sfera ◽  
Carolina Osorio ◽  
Leah Rahman ◽  
Carlos Manuel Zapata-Martín del Campo ◽  
Jose Campo Maldonado ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Medial Prefrontal Cortex ◽  
Neurotrophic Factor ◽  
Ang Ii ◽  
Sigma 1 ◽  
Trauma Processing ◽  
The Brain ◽  
Increased Susceptibility

Graphical Abstract 1Covid-19 triggers endothelial cell (EC) senescence and dysfunction, likely predisposing to PTSD by increasing microvascular permeability that enables the extravasation of stress molecules into the brain trauma-processing networks in amygdala, hippocampus and the medial prefrontal cortex. The virus upregulates host angiotensin II (ANG II) (via S1 antigen), usurps furin/plasmin (via S2 antigen), mitochondria (via ORF9b), and Sigma-1 receptors (Sig-1Rs) via NSP6. These structures, previously associated with PTSD, link the SARS-CoV-2 virus to increased susceptibility for stress related disorders. As ECs are major producers of brain derived neurotrophic factor (BDNF), a neurotrophin altered in PTSD, senescent ECs lower this molecule further, predisposing to stress related disorders.

scholarly journals Update on angiotensin II: new endocrine connections between the brain, adrenal glands and the cardiovascular system

2017 ◽  
Vol 6 (7) ◽  
pp. R131-R145 ◽  
Author(s):  
Frans H H Leenen ◽  
Mordecai P Blaustein ◽  
John M Hamlyn
Keyword(s):  
Angiotensin Ii ◽  
Sympathetic Activity ◽  
Endocrine Function ◽  
Lv Function ◽  
Slow Pathway ◽  
Ang Ii ◽  
Endogenous Ouabain ◽  
Plasma Angiotensin ◽  
Synthase Inhibitor ◽  
The Brain

In the brain, angiotensinergic pathways play a major role in chronic regulation of cardiovascular and electrolyte homeostasis. Increases in plasma angiotensin II (Ang II), aldosterone, [Na+] and cytokines can directly activate these pathways. Chronically, these stimuli also activate a slow neuromodulatory pathway involving local aldosterone, mineralocorticoid receptors (MRs), epithelial sodium channels and endogenous ouabain (EO). This pathway increases AT1R and NADPH oxidase subunits and maintains/further increases the activity of angiotensinergic pathways. These brain pathways not only increase the setpoint of sympathetic activity per se, but also enhance its effectiveness by increasing plasma EO and EO-dependent reprogramming of arterial and cardiac function. Blockade of any step in this slow pathway or of AT1R prevents Ang II-, aldosterone- or salt and renal injury-induced forms of hypertension. MR/AT1R activation in the CNS also contributes to the activation of sympathetic activity, the circulatory and cardiac RAAS and increase in circulating cytokines in HF post MI. Chronic central infusion of an aldosterone synthase inhibitor, MR blocker or AT1R blocker prevents a major part of the structural remodeling of the heart and the decrease in LV function post MI, indicating that MR activation in the CNS post MI depends on aldosterone, locally produced in the CNS. Thus, Ang II, aldosterone and EO are not simply circulating hormones that act on the CNS but rather they are also paracrine neurohormones, locally produced in the CNS, that exert powerful effects in key CNS pathways involved in the long-term control of sympathetic and neuro-endocrine function and cardiovascular homeostasis.

scholarly journals Skeletal muscle-endothelial cell cross talk through angiotensin II

2010 ◽  
Vol 299 (6) ◽  
pp. C1402-C1408 ◽  
Author(s):  
Leeann M. Bellamy ◽  
Adam P. W. Johnston ◽  
Michael De Lisio ◽  
Gianni Parise
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Branch Point ◽  
Endothelial Cell Migration ◽  
Tube Length ◽  
Ang Ii

The role of angiotensin II (ANG II) in postnatal vasculogenesis and angiogenesis during skeletal muscle (SKM) regeneration is unknown. We examined the capacity of ANG II to stimulate capillary formation and growth during cardiotoxin-induced muscle regeneration in ACE inhibitor-treated ANG II type 1a receptor knockout (AT1a−/−) and C57Bl/6 control mice. Analysis of tibialis anterior (TA) cross-sections revealed 17% and 23% reductions in capillarization in AT1a−/− and captopril treated mice, respectively, when compared with controls, 21 days postinjury. Conversely, no differences in capillarization were detected at early time points (7 and 10 days). These results identify ANG II as a regulator of angiogenesis but not vasculogenesis in vivo. In vitro angiogenesis assays of human umbilical vein endothelial cells (HUVECs) further confirmed ANG II as proangiogeneic as 71% and 124% increases in tube length and branch point number were observed following ANG II treatment. Importantly, treatment of HUVECs with conditioned media from differentiated muscle cells resulted in an 84% and 203% increase in tube length and branch point number compared with controls, which was abolished following pretreatment of the cells with an angiotensin-converting enzyme inhibitor. The pro-angiogenic effect of ANG II can be attributed to an enhanced endothelial cell migration because both transwell and under agarose migration assays revealed a 37% and 101% increase in cell motility, respectively. Collectively, these data highlight ANG II as a proangiogenic regulator during SKM regeneration in vivo and more importantly demonstrates that ANG II released from SKM can signal endothelial cells and regulate angiogenesis through the induction of endothelial cell migration.

scholarly journals Central interactions of aldosterone and angiotensin II in aldosterone- and angiotensin II-induced hypertension

2011 ◽  
Vol 300 (2) ◽  
pp. H555-H564 ◽  
Author(s):  
Baojian Xue ◽  
Terry G. Beltz ◽  
Yang Yu ◽  
Fang Guo ◽  
Celso E. Gomez-Sanchez ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Oxidase Inhibitor ◽  
Male Rats ◽  
Ang Ii ◽  
Adeno Associated Virus ◽  
Synergistic Interactions ◽  
Induced Hypertension ◽  
Ros Scavenger ◽  
The Brain

Many studies have implicated both angiotensin II (ANG II) and aldosterone (Aldo) in the pathogenesis of hypertension, the progression of renal injury, and cardiac remodeling after myocardial infarction. In several cases, ANG II and Aldo have been shown to have synergistic interactions in the periphery. In the present studies, we tested the hypothesis that ANG II and Aldo interact centrally in Aldo- and ANG II-induced hypertension in male rats. In rats with blood pressure (BP) and heart rate (HR) measured by DSI telemetry, intracerebroventricular (icv) infusions of the mineralocorticoid receptor (MR) antagonists spironolactone and RU28318 or the angiotensin type 1 receptor (AT1R) antagonist irbesartan significantly inhibited Aldo-induced hypertension. In ANG II-induced hypertension, icv infusion of RU28318 significantly reduced the increase in BP. Moreover, icv infusions of the reactive oxygen species (ROS) scavenger tempol or the NADPH oxidase inhibitor apocynin attenuated Aldo-induced hypertension. To confirm these effects of pharmacological antagonists, icv injections of either recombinant adeno-associated virus carrying siRNA silencers of AT1aR (AT1aR-siRNA) or MR (MR-siRNA) significantly attenuated the development of Aldo-induced hypertension. The immunohistochemical and Western blot analyses of AT1aR-siRNA- or MR-siRNA-injected rats showed a marked reduction in the expression of AT1R or MR in the paraventricular nucleus compared with scrambled siRNA rats. When animals from all studies underwent ganglionic blockade with hexamethonium, there was a smaller reduction in the fall of BP in animals receiving icv AT1R or MR antagonists. These results suggest that ANG II and Aldo interact in the brain in a mutually cooperative manner such that the functional integrity of both brain AT1R and MR are necessary for hypertension to be induced by either systemic ANG II or Aldo. The pressor effects produced by systemic ANG II or Aldo involve increased central ROS and sympathetic outflow.

Angiotensin II receptors in SFO but not in OVLT mediate isoproterenol-induced thirst

1994 ◽  
Vol 267 (1) ◽  
pp. R7-R15 ◽  
Author(s):  
D. A. Fitts
Keyword(s):  
Angiotensin Ii ◽  
Circumventricular Organs ◽  
Ang Ii ◽  
Circumventricular Organ ◽  
Adrenergic Agonist ◽  
Receptor Sites ◽  
Organum Vasculosum Laminae Terminalis ◽  
Reduced Drinking ◽  
Beta Adrenergic Agonist ◽  
The Brain

Thirst elicited by the beta-adrenergic agonist isoproterenol in rats depends in part on the secretion of renin, the consequent synthesis of angiotensin II (ANG II), and the binding of circulating ANG II to dipsogenic receptors in the brain. These receptors probably reside in either of two forebrain circumventricular organs, the subfornical organ (SFO) or organum vasculosum laminae terminalis (OVLT). Experiments determined that lesions of the SFO, but not of the OVLT, reduced drinking induced by isoproterenol treatment. Competitive ANG II-receptor antagonism with sarthran reduced isoproterenol-induced drinking when the blocker was infused into the SFO but not when it was infused into the OVLT or into the lateral ventricles at a 25-fold greater dose. The findings confirm the widely held belief that renin-dependent thirst elicited by isoproterenol relies on ANG II binding to receptor sites at a circumventricular organ in the brain. The results demonstrate that this site is the SFO and not the OVLT.

scholarly journals Autophagy inhibition by chloroquine prevents increase in blood pressure and preserves endothelial functions

2020 ◽  
Vol 19 (4) ◽  
pp. 789-796
Author(s):  
Moon Jain ◽  
Hina Iqbal ◽  
Pankaj Yadav ◽  
Himalaya Singh ◽  
Debabrata Chanda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Autophagy Flux ◽  
Endothelial Functions

Purpose: To determine the effects of lysosomal inhibition of autophagy by chloroquine (CHQ) onhypertension-associated changes in the endothelial functions. Method: Angiotensin II (Ang II)-treated human endothelial cell line EA.hy926 and renovascularhypertensive rats were subjected to CHQ treatment (in vitro: 0.5, 1, and 2.5 μM; in vivo: 50 mg/kg/dayfor three weeks). Changes in the protein expressions of LC3b II (autophagosome formation marker) andp62 (autophagy flux marker) were assessed using immunoblotting. Cell migration assay, tubuleformation assay (in vitro), and organ bath studies (in vivo) were performed to evaluate the endothelialfunctions. Hemodynamic parameters were measured as well. Results: A higher expression of LC3b II and a reduced expression of p62 observed in the Ang II-treatedendothelial cells, as well as in the aorta of the hypertensive rats, indicated enhanced autophagy.Treatment with CHQ resulted in reduced autophagy flux (in vitro as well as in vivo) and suppressed AngII-induced endothelial cell migration and angiogenesis (in vitro). The treatment with CHQ was alsoobserved to prevent increase in blood pressure in hypertensive rats and preserved acetylcholineinducedrelaxation in phenylephrine-contracted aorta from the hypertensive rats. In addition, chloroquineattenuated Ang II-induced contractions in the aorta of normotensive as well as hypertensive rats. Conclusion: These observations indicated that CHQ lowers the blood pressure and preserves thevascular endothelial function during hypertension. Keywords: Angiotensin II, Autophagy, Chloroquine, Endothelial function, Hypertension, Vasculardysfunction

Laser technique for anatomical-functional study of the medial prefrontal cortex of the brain

1999 ◽  
Author(s):  
Laura Sanchez-Huerta ◽  
Adan Hernandez ◽  
Griselda Ayala ◽  
Javier Marroquin ◽  
Adriana B. Silva ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Functional Study ◽  
Laser Technique ◽  
The Brain

scholarly journals mTORC1 Signaling Contributes to Drinking But Not Blood Pressure Responses to Brain Angiotensin II

Endocrinology ◽  
2016 ◽  
Vol 157 (8) ◽  
pp. 3140-3148 ◽  
Author(s):  
Kenjiro Muta ◽  
Donald A. Morgan ◽  
Justin L. Grobe ◽  
Curt D. Sigmund ◽  
Kamal Rahmouni
Keyword(s):  
Angiotensin Ii ◽  
Water Intake ◽  
Drinking Behavior ◽  
Subfornical Organ ◽  
Dependent Manner ◽  
Ang Ii ◽  
Mtorc1 Signaling ◽  
Wide Range ◽  
The Brain

Mechanistic target of rapamycin complex 1 (mTORC1) is a molecular node that couples extracellular cues to a wide range of cellular events controlling various physiological processes. Here, we identified mTORC1 signaling as a critical mediator of angiotensin II (Ang II) action in the brain. In neuronal GT1–7 cells, we show that Ang II stimulates neuronal mTORC1 signaling in an Ang II type 1 receptor-dependent manner. In mice, a single intracerebroventricular (ICV) injection or chronic sc infusion of Ang II activated mTORC1 signaling in the subfornical organ, a critical brain region in cardiovascular control and fluid balance. Moreover, transgenic sRA mice with brain-specific overproduction of Ang II displayed increased mTORC1 signaling in the subfornical organ. To test the functional role of brain mTORC1 in mediating the action of Ang II, we examined the consequence of mTORC1 inhibition with rapamycin on Ang II-induced increase in water intake and arterial pressure. ICV pretreatment with rapamycin blocked ICV Ang II-mediated increases in the frequency, duration, and amount of water intake but did not interfere with the pressor response evoked by Ang II. In addition, ICV delivery of rapamycin significantly reduced polydipsia, but not hypertension, of sRA mice. These results demonstrate that mTORC1 is a novel downstream pathway of Ang II type 1 receptor signaling in the brain and selectively mediates the effect of Ang II on drinking behavior.

scholarly journals Choice-dependent cross-modal interaction in the medial prefrontal cortex of rats

2021 ◽  
Author(s):  
Mengyao Zheng ◽  
Jinghong Xu ◽  
Les Keniston ◽  
Jing Wu ◽  
Song Chang ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Simultaneous Presentation ◽  
Enhancement Effect ◽  
Modal Interaction ◽  
Visual Cue ◽  
Neural Activities ◽  
Forced Choice Tasks ◽  
Choice Tasks ◽  
The Brain

Abstract Cross-modal interaction (CMI) could significantly influence the perceptional or decision-making process in many circumstances. However, it remains poorly understood what integrative strategies are employed by the brain to deal with different task contexts. To explore it, we examined neural activities of the medial prefrontal cortex (mPFC) of rats performing cue-guided two-alternative forced-choice tasks. In a task requiring rats to discriminate stimuli based on auditory cue, the simultaneous presentation of an uninformative visual cue substantially strengthened mPFC neurons' capability of auditory discrimination mainly through enhancing the response to the preferred cue. Doing this also increased the number of neurons revealing a cue preference. If the task was changed slightly and a visual cue, like the auditory, denoted a specific behavioral direction, mPFC neurons frequently showed a different CMI pattern with an effect of cross-modal enhancement best evoked in information-congruent multisensory trials. In a choice free task, however, the majority of neurons failed to show a cross-modal enhancement effect and cue preference. These results indicate that CMI at the neuronal level is context-dependent in a way that differs from what has been shown in previous studies.

Sign in / Sign up

Export Citation Format

Share Document