Abstract 459: Vasoactivity of the Alzheimer ß-Amyloid Peptides is Mediated by an Activation of the a 1 -Adrenoreceptor

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Nadine Haase ◽  
Florian Herse ◽  
Bastian Spallek ◽  
Hannelore Haase ◽  
Gerd Wallukat ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Adrenergic Receptor ◽  
Ex Vivo ◽  
Receptor Activation ◽  
Negative Control ◽  
Amyloid Peptide ◽  
Receptor Blocker ◽  
Ex Vivo Model ◽  
Aβ Amyloid

Alzheimer disease (AD) features β-amyloid peptide (Aβ) deposition in brain and blood vessels and is associated with hypertension. Aβ can cause vasoconstriction and endothelial dysfunction. Recently, we could show that Aβ peptides elicit a signal transduction pathway in vascular smooth muscle cells and cardiomyocytes, induced by α 1 -adrenergic receptor activation. We hypothesized that the Aβ vasoactivity is also induced by activation of the α 1 -adrenoreceptor. Mouse aortic Rings were incubated for 24 h with 1 μmol/l Aβ (25-35). The influence of Aβ (25-35) on vasoconstriction of mouse aortic rings was studied in the additional presence and absence of α 1 -adrenergic receptor blocker prazosin. Vasoactivity in isolated aortic rings was measured using an isometric myograph. Vasoconstriction to 5-hydroxytryptamine was significantly increased (P≤0.001) in aortic rings by Aβ (25-35) pretreatment. This vasoactive effect was improved by the presence of α 1 -adrenergic receptor blocker during the Aβ (25-35) pretreatment. Rat middle cerebral artery (MCA) segments were treated with either 0.1μmol/L Aβ (25-35) or 0.1μmol/L of a negative control peptide with a reverse amino acid sequence (Aβ rev.) of Aβ (25-35) for 4h. Constriction of the middle cerebral artery was measured in dual vessel chamber. Incubation with Aβ (25-35) significantly enhanced (P≤0.0005) response of middle cerebral artery segments to the α 1 -agonist phenylephrine induced contractions. In a further ex vivo model of Langendorff-perfused rat hearts Aβ (25-35) also induced vasoconstriction of coronary arteries that resulted in decreased coronary flow. These effects could also be reversed by α 1 -adrenergic receptor blockade. Furthermore we analyzed the brain of hypertensive dTGR animals and in human arteriosclerotic plaques for the presence of Aβ amyloid. Amyloid deposits are present in cerebral cortex of hypertensive dTGR animals with damaged blood-brain barrier and in human arteriosclerotic plaques. Our data are relevant to the association between AD and hypertension. They may serve to explain impaired of vascular responses by Aβ and could have therapeutic implications.

U-46619 but not serotonin increases endocannabinoid content in middle cerebral artery: evidence for functional relevance

2005 ◽  
Vol 288 (6) ◽  
pp. H2694-H2701 ◽  
Author(s):  
David J. Rademacher ◽  
Sachin Patel ◽  
W.-S. Vanessa Ho ◽  
Amanda M. Savoie ◽  
Nancy J. Rusch ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
Cerebral Arteries ◽  
Receptor Activation ◽  
Maximal Effect ◽  
Receptor Antagonists ◽  
Local Formation ◽  
Sr 141716

Cerebral vascular smooth muscle cells express the CB1 cannabinoid receptor, and CB1 receptor agonists produce vasodilation of cerebral arteries. The purpose of this study was to determine whether vasoconstriction of rat middle cerebral artery (MCA) results in the local formation of endocannabinoids (eCBs), which, via activation of CB1 receptors, oppose the vasoconstriction in a feedback manner. The thromboxane A2 (TXA2) mimetic U-46619 significantly increased N-arachidonylethanolamine (AEA) and 2-arachidonylglycerol (2-AG) content of isolated MCA, whereas 5-hydroxytrypamine (5-HT) decreased AEA and 2-AG content. If eCBs play a feedback role in the regulation of MCA tone, then CB1 receptor antagonists should enhance the constriction of MCA produced by U-46619 but not 5-HT. U-46619 caused concentration-dependent constrictions of endothelium-denuded MCA. Two CB1 receptor antagonists SR-141716 and AM-251 decreased the EC50 value for U-46619 to constrict endothelium-denuded MCA without affecting the maximal effect. A low concentration of CB1 receptor agonist Win-55212-2 (30 nM) produced vasodilation of MCAs constricted with low but not saturating concentrations of U-46619. SR-141716 had no effect on the 5-HT concentration-contraction relationship. These data suggest that TXA2 receptor activation increases MCA eCB content, which, via activation of CB1 receptors, reduces the constriction produced by moderate concentrations of the TXA2 agonist. Although 5-HT-induced vasoconstriction is reduced by exogenous CB1 receptor agonist, activation of 5-HT receptors does not increase eCB content. These results suggest that MCA production of eCBs is not regulated by constriction per se but likely via a signaling pathway that is specific for TXA2 receptors and not 5-HT receptors.

scholarly journals An Increase in Murine Skeletal Muscle Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α (PGC-1α) mRNA in Response to Exercise Is Mediated by β-Adrenergic Receptor Activation

Endocrinology ◽  
2007 ◽  
Vol 148 (7) ◽  
pp. 3441-3448 ◽  
Author(s):  
Shinji Miura ◽  
Kentaro Kawanaka ◽  
Yuko Kai ◽  
Mayumi Tamura ◽  
Masahide Goto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Adrenergic Receptor ◽  
Ex Vivo ◽  
Specific Inhibitor ◽  
Receptor Activation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose ◽  
Exercise Induced

A single bout of exercise increases expression of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α mRNA, which may promote mitochondrial biogenesis in skeletal muscle. In brown adipose tissue, cold exposure up-regulates PGC-1α expression via adrenergic receptor (AR) activation. Because exercise also activates the sympathetic nervous system, we examined whether exercise-induced increase in PGC-1α mRNA expression in skeletal muscle was mediated via AR activation. In C57BL/6J mice, injection of the β2-AR agonist clenbuterol, but not α-, β1-, or β3-AR agonists, increased PGC-1α mRNA expression more than 30-fold in skeletal muscle. The clenbuterol-induced increase in PGC-1α mRNA expression in mice was inhibited by pretreatment with the β-AR antagonist propranolol. In ex vivo experiments, direct exposure of rat epitrochlearis to β2-AR agonist, but not α-, β1-, and β3-AR agonist, led to an increase in levels of PGC-1α mRNA. Injection of β2-AR agonist did not increase PGC-1α mRNA expression in β1-, β2-, and β3-AR knockout mice (β-less mice). PGC-1α mRNA in gastrocnemius was increased 3.5-fold in response to running on a treadmill for 45 min. The exercise-induced increase in PGC-1α mRNA was inhibited by approximately 70% by propranolol or the β2-AR-specific inhibitor ICI 118,551. The exercise-induced increase in PGC-1α mRNA in β-less mice was also 36% lower than that in wild-type mice. These data indicate that up-regulation of PGC-1α expression in skeletal muscle by exercise is mediated, at least in part, by β-ARs activation. Among ARs, β2-AR may mediate an increase in PGC-1α by exercise.

scholarly journals Systemic β-Adrenergic Receptor Activation Augments the ex vivo Expansion and Anti-Tumor Activity of Vγ9Vδ2 T-Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Forrest L. Baker ◽  
Austin B. Bigley ◽  
Nadia H. Agha ◽  
Charles R. Pedlar ◽  
Daniel P. O'Connor ◽  
...  
Keyword(s):  
T Cells ◽  
Adrenergic Receptor ◽  
Ex Vivo ◽  
Receptor Activation ◽  
Ex Vivo Expansion ◽  
Vγ9vδ2 T Cells ◽  
Anti Tumor Activity

Abstract TMP115: Nox-2 and Cerebrovascular Function in Metabolic Syndrome After a Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Paul D Chantler ◽  
Stephen D Brooks ◽  
Kayla W Branyan ◽  
Shin Asano ◽  
Xuefang Ren ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Ex Vivo ◽  
Specific Inhibitor ◽  
Stroke Severity ◽  
Post Stroke ◽  
Cerebrovascular Function ◽  
No Bioavailability

Introduction: The aim here is to elucidate the mechanisms involved in post-stroke cerebrovascular impairments in metabolic syndrome (MetS) that pre-dispose obese patients to more severe post-stroke deficits. Methods: 1 hr middle cerebral artery occlusion was performed in 17 week old lean (LZR) and obese Zucker (OZR: MetS model) rats. At 24 hr or 15 days post-stroke, the ipsilateral middle cerebral artery (MCA) was cannulated in an ex-vivo microvessel preparation to examine MCA reactivity. Cerebrovascular microvessel density (MVD) was examined 15 days post-stroke via IHC. To examine a potential role of Nox2 and oxidative stress, a specific inhibitor of Nox2 oxidase Nox2-dstat (i.p 10mg/kg) was given during the stroke procedure in OZR. Results: In LZR, MCA reactivity was impaired vs. non-stroke control at 24hr post-stroke and remained stable at 15 days post-stroke. In LZR, NO bioavailability was reduced at 24hrs vs. controls, which remained stable at 15 days. In OZR, the MCA impairment was greater at 24 hr vs. LZR, and worsened significantly at 15 days post stroke. NO bioavailability for OZR at 24 hr was similar to LZR stroke, but by 15 days had fallen. MVD was reduced 15 days post-stroke, with a larger loss in OZR vs. LZR. Stroke mortality and infarct size were higher for OZR. Nox2 inhibition restored MCA reactivity, improved MVD and NO levels, and limited stroke infarct size in OZR post-stroke. Discussion: Our data suggest that the MetS increases stroke severity and drives a progressive decline in cerebrovascular dysfunction following ischemic stroke. Inhibiting Nox2 production improved stroke outcome in MetS.

Superficial Temporal Artery–Middle Cerebral Artery Bypass Ex Vivo Hybrid Simulator: Face, Content, Construct, and Concurrent Validity

2020 ◽  
Vol 142 ◽  
pp. e378-e384
Author(s):  
Carlos E. Ferrarez ◽  
Raphael Bertani ◽  
Doralice M. Leite Batista ◽  
Renan Lovato ◽  
Caio Perret ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Concurrent Validity ◽  
Ex Vivo ◽  
Artery Bypass ◽  
Superficial Temporal Artery ◽  
Temporal Artery ◽  
Hybrid Simulator

Pre- and postjunctional α2-adrenergic receptors in fetal and adult ovine cerebral arteries

2002 ◽  
Vol 282 (6) ◽  
pp. R1654-R1662 ◽  
Author(s):  
John M. Bishai ◽  
Luit Penninga ◽  
Roel Nijland ◽  
Rogier Meulenaar ◽  
Ciprian P. Gheorghe ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Dose Response ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cerebral Arteries ◽  
Age Groups ◽  
Significant Component ◽  
Contractile Responses ◽  
Developmental Age

In ovine cerebral arteries, adrenergic-mediated vasoconstrictor responses differ significantly with developmental age. We tested the hypothesis that, in part, these differences are a consequence of altered α2-adrenergic receptor (α2-AR) density and/or affinity. In fetal (∼140 days) and adult sheep, we measured α2-AR density and affinity with the antagonist [3H]idazoxan in main branch cerebral arteries and other vessels. We also quantified contractile responses in middle cerebral artery (MCA) to norepinephrine (NE) or phenylephrine in the presence of the α2-AR antagonists yohimbine and idazoxan and contractile responses to the α2-AR agonists clonidine and UK-14304. In fetal and adult cerebral artery homogenates, α2-AR density was 201 ± 18 and 52 ± 6 fmol/mg protein, respectively ( P< 0.01); however, antagonist affinity values did not differ. In fetal, but not adult, MCA, 10−7 M yohimbine significantly decreased the pD2 for NE-induced tension in the presence of 3 × 10−5 M cocaine, 10−5 M deoxycorticosterone, and 10−6 M tetrodotoxin. In fetal, but not adult, MCA, UK-14304 induced a significant decrease in pD2 for the phenylephrine dose-response relation. In addition, stimulation-evoked fractional NE release was significantly greater in fetal than in adult cerebral arteries. In the presence of 10−6 M idazoxan to block α2-AR-mediated inhibition of prejunctional NE release, the fractional NE release was significantly increased in both age groups. We conclude that in fetal and adult ovine cerebral arteries, α2-AR appear to be chiefly prejunctional. Nonetheless, the fetal cerebral arteries appear to have a significant component of postjunctional α2-AR.

Endothelial TrkB receptor activation controls vascular tone of rat middle cerebral artery

2021 ◽  
pp. 106930
Author(s):  
P. Totoson ◽  
C. Santini ◽  
A. Tessier ◽  
C. Marie ◽  
C. Demougeot
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Vascular Tone ◽  
Receptor Activation ◽  
Trkb Receptor
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