Amyloid-β peptides activate α1-adrenergic cardiovascular receptors


  • N. Haase
  • F. Herse
  • B. Spallek
  • H. Haase
  • I. Morano
  • F. Qadri
  • I.A. Szijártó
  • I. Rohm
  • A. Yilmaz
  • J.P. Warrington
  • M.J. Ryan
  • M. Gollasch
  • D.N. Müller
  • R. Dechend
  • G. Wallukat


  • Hypertension


  • Hypertension 62 (5): 966-972


  • 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.