In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 62, No. suppl_1 ( 2013-09)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/hyp.62.suppl_1.A459
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2013
ZDB Id:
2094210-2
