Amyloid-β peptides activate α1-adrenergic cardiovascular receptors

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Item Type:	Article
Title:	Amyloid-β peptides activate α1-adrenergic cardiovascular receptors
Creators Name:	Haase, N., Herse, F., Spallek, B., Haase, H., Morano, I., Qadri, F., Szijártó, I.A., Rohm, I., Yilmaz, A., Warrington, J.P., Ryan, M.J., Gollasch, M., Müller, D.N., Dechend, R. and Wallukat, G.
Abstract:	Alzheimer disease features amyloid-beta (Abeta) peptide deposition in brain and blood vessels and is associated with hypertension. Abeta peptide can cause vasoconstriction and endothelial dysfunction. We observed that Abeta peptides exert a chronotropic effect in neonatal cardiomyocytes, similar to alpha1-adrenergic receptor autoantibodies that we described earlier. Recently, it was shown that alpha1-adrenergic receptor could impair blood-brain flow. We hypothesized that Abeta peptides might elicit a signal transduction pathway in vascular cells, induced by alpha1-adrenergic receptor activation. Abeta (25-35) and Abeta (10-35) induced a positive chronotropic effect in the cardiac contraction assay (28.75+/-1.15 and 29.40+/-0.98 bpm), which was attenuated by alpha1-adrenergic receptor blockers (urapidil, 1.53+/-1.17 bpm; prazosin, 0.30+/-0.96 bpm). Both Abeta peptides induced an intracellular calcium release in vascular smooth muscle cells. Chronotropic activity and calcium response elicited by Abeta (25-35) were blocked with peptides corresponding to the first extracellular loop of the alpha1-adrenergic receptor. We observed an induction of extracellular-regulated kinase 1/2 phosphorylation by Abeta (25-35) in Chinese hamster ovary cells overexpressing alpha1-adrenergic receptor, vascular smooth muscle cells, and cardiomyocytes. We generated an activation-state-sensitive alpha1-adrenergic receptor antibody and visualized activation of the alpha1-adrenergic receptor by Abeta peptide. Abeta (25-35) induced vasoconstriction of mouse aortic rings and in coronary arteries in Langendorff-perfused rat hearts that resulted in decreased coronary flow. Both effects could be reversed by alpha1-adrenergic receptor blockade. Our data are relevant to the association between Alzheimer disease and hypertension. They may explain impairment of vascular responses by Abeta and could have therapeutic implications.
Keywords:	{alpha}1-Adrenergic Receptor, Alzheimer Disease, Amyloid-{beta} Peptides, Hypertension, Signal Transduction, Vasoconstriction, Animals, Cricetinae, Mice, Rats
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	62
Number:	5
Page Range:	966-972
Date:	November 2013
Official Publication:	https://doi.org/10.1161/HYPERTENSIONAHA.113.01348
PubMed:	View item in PubMed

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