scholarly journals SARS-CoV-2 binding to ACE2 triggers pericyte-mediated angiotensin-evoked cerebral capillary constriction

2021 ◽  
Author(s):  
Chanawee Hirunpattarasilp ◽  
Gregory James ◽  
Felipe Freitas ◽  
Huma Sethi ◽  
Josef T Kittler ◽  
...  
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Brain Slices ◽  
Receptor Binding Domain ◽  
Receptor Blockers ◽  
Kidney Blood Flow ◽  
Cerebral Capillary ◽  
At1 Receptor Blockers ◽  
The Brain ◽  
Cortical Slices

The SARS-CoV-2 receptor, ACE2, is found on pericytes, contractile cells enwrapping capillaries that regulate brain, heart and kidney blood flow. ACE2 converts vasoconstricting angiotensin II into vasodilating angiotensin-(1-7). In brain slices from hamster, which has an ACE2 sequence similar to human ACE2, angiotensin II alone evoked only a small capillary constriction, but evoked a large pericyte-mediated capillary constriction generated by AT1 receptors in the presence of the SARS-CoV-2 receptor binding domain (RBD). The effect of the RBD was mimicked by blocking ACE2. A mutated non-binding RBD did not potentiate constriction. A similar RBD-potentiated capillary constriction occurred in human cortical slices. This constriction reflects an RBD-induced decrease in the conversion of angiotensin II to angiotensin-(1-7). The clinically-used drug losartan inhibited the RBD-potentiated constriction. Thus AT1 receptor blockers could be protective in SARS-CoV-2 infection by reducing pericyte-mediated blood flow reductions in the brain, and perhaps the heart and kidney.

scholarly journals (Pro)renin receptor: another member of the system controlled by angiotensin II?

2011 ◽  
Vol 13 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Luciana G Pereira ◽  
Carine P Arnoni ◽  
Edgar Maquigussa ◽  
Priscila C Cristovam ◽  
Juliana Dreyfuss ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Mesangial Cells ◽  
At1 Receptor ◽  
Receptor Internalization ◽  
Prorenin Receptor ◽  
Receptor Blockers ◽  
And Function ◽  
At1 Receptor Blockers

The prorenin receptor [(P)RR] is upregulated in the diabetic kidney and has been implicated in the high glucose (HG)-induced overproduction of profibrotic molecules by mesangial cells (MCs), which is mediated by ERK1/2 phosphorylation. The regulation of (P)RR gene transcription and the mechanisms by which HG increases (P)RR gene expression are not fully understood. Because intracellular levels of angiotensin II (AngII) are increased in MCs stimulated with HG, we used this in vitro system to evaluate the possible role of AngII in (P)RR gene expression and function by comparing the effects of AT1 receptor blockers (losartan or candesartan) and (P)RR mRNA silencing (siRNA) in human MCs (HMCs) stimulated with HG. HG induced an increase in (P)RR and fibronectin expression and in ERK1/2 phosphorylation. These effects were completely reversed by (P)RR siRNA and losartan but not by candesartan (an angiotensin receptor blocker that, in contrast to losartan, blocks AT1 receptor internalization). These results suggest that (P)RR gene activity may be controlled by intracellular AngII and that HG-induced ERK1/2 phosphorylation and fibronectin overproduction are primarily induced by (P)RR activation. This relationship between AngII and (P)RR may constitute an additional pathway of MC dysfunction in response to HG stimulation.

Is it Possible to Differentiate between Angiotensin II Type 1 (AT1) Receptor Blockers in Normotensive Volunteers?

2000 ◽  
Vol 9 (sup1) ◽  
pp. 53-53
Author(s):  
M. AZIZI, ◽  
G. CHATELLIER, ◽  
L. NICOLET, ◽  
T. GUYENE, ◽  
J. HEMPENIUS, ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
At1 Receptor ◽  
Receptor Blockers ◽  
At1 Receptor Blockers

Ex Vivo MuEtinuciear NMR Spectroscopy of Perfused, Respiring Rat Brain Slices: Model Studies of Hypoxia, Ischemia, and Excitotoxscit

1997 ◽  
Author(s):  
L. Litt ◽  
M.T. Espanol
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nmr Spectroscopy ◽  
Clinical Care ◽  
Brain Slices ◽  
In Vivo Nmr ◽  
In Vivo Nmr Spectroscopy ◽  
Permanent Brain Damage ◽  
The Brain

We believe there are important roles for in vivo NMR spectroscopy techniques in studies of protection and treatment in stroke. Perhaps the primary utility of in vivo NMR spectroscopy is to establish the relevance of metabolic integrity, intracellular pH, and intracellular energy stores to concurrent changes occurring both at gross physiological levels (e.g., changes in cerebral blood flow, or blood oxygenation), and at microscopic or cellular levels. It has long been known that the brain is exquisitely sensitive to deprivations of oxygen, glucose, and cerebral blood flow. Routine human surgery on a limb takes place every day with tourniquets stopping all blood flow for up to two hours. In contrast, the deprivation of all blood flow to the brain (global ischemia) for approximately 5 minutes can result in severe, permanent brain damage. Research has gone on for more than 30 years to understand why the brain’s revival time is so much shorter, and to discover brain biochemical interventions that might dramatically extend the brain’s intolerance beyond 5 minutes, and therefore be relevant to protection and treatment of stroke. (Kogure and Hossmann, 1985; 1993) Stroke, defined as a permanent neurologic deficit arising from the death of brain cells, kills ∼ 150,000 people in the U.S.A. each year, and is the third leading cause of death (Feinleib et al., 1993). It is the next malady to escape, once one has dodged death from cardiovascular disease and cancer. Many, if not most, U.S.A. stroke victims will receive neurological clinical care not substantially different from what was provided 30 years ago. Most stroke patients will be put in intensive care units where blood pressure will be regulated and kept in a “safe” range, with the body given supportive care and the brain given an opportunity to heal itself. The problem of stroke is actually quite complex because there are several different kinds of stroke (ischemic, hemorrhagic, etc.), and because numerous systemic physiological factors are of relevance. Nevertheless, exciting advances in brain biochemistry suggest that stroke therapy and prophylaxis axe likely to improve dramatically in the near future (Zivin and Choi, 1991).

scholarly journals Facile and Efficient Syntheses of a Series of N-Benzyl and N-Biphenylmethyl Substituted Imidazole Derivatives Based on (E)-Urocanic acid, as Angiotensin II AT1 Receptor Blockers

Molecules ◽  
2013 ◽  
Vol 18 (7) ◽  
pp. 7510-7532 ◽  
Author(s):  
George Agelis ◽  
Konstantinos Kelaidonis ◽  
Amalia Resvani ◽  
Dimitra Kalavrizioti ◽  
Maria-Eleni Androutsou ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
At1 Receptor ◽  
Urocanic Acid ◽  
Imidazole Derivatives ◽  
Receptor Blockers ◽  
At1 Receptor Blockers

Role of Angiotensin II AT1 Receptor Blockers in the Treatment of Arterial Hypertension

2003 ◽  
Vol 10 (6) ◽  
pp. 401-408 ◽  
Author(s):  
Freddy Contreras ◽  
Mar??a Antonia de la Parte ◽  
Julio Cabrera ◽  
Nestor Ospino ◽  
Zafar H. Israili ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Arterial Hypertension ◽  
At1 Receptor ◽  
Receptor Blockers ◽  
At1 Receptor Blockers

Effect of Withdrawal from Chronic Ethanol Ingestion on the cAMP Response of Cerebral Cortical Slices Using the Agonists Histamine, Serotonin, and Other Neurotransmitters

1975 ◽  
Vol 53 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Samuel W. French ◽  
Douglas S. Palmer ◽  
Mary E. Narod
Keyword(s):  
Brain Slices ◽  
Ethanol Withdrawal ◽  
Aminobutyric Acid ◽  
Ethanol Ingestion ◽  
Evoked Responses ◽  
Alternative Hypotheses ◽  
Adrenergic Antagonists ◽  
The Brain ◽  
Cortical Slices

The effect of ethanol withdrawal on the cAMP response of cerebral cortical brain slices was studied. The cAMP response was evoked in vitro by various neurotransmitters including norepinephrine (NE), histamine, serotonin, dopamine, acetylcholine, and γ-aminobutyric acid (GABA). The cAMP response to NE and histamine was enhanced by ethanol withdrawal. Serotonin evoked a cAMP response in the brain slices from ethanol-withdrawal rats but not in pair-fed controls. The histamine and serotonin evoked responses were blocked by chlortripolon and methysergide, respectively. The responses to histamine and serotonin were also blocked by a- and β-adrenergic antagonists, possibly because of the nonspecific membrane stabilizing effect of these antagonists. GABA inhibited the NE stimulated cAMP response possibly through the hyperpolarizing action of GABA. The results support the hypothesis that ethanol withdrawal induces a nonspecific postjunctional supersensitivity. It is postulated that the supersensitivity involves a partial depolarization of the receptor membrane. Alternative hypotheses are reviewed.

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