Amyloid-β Peptides Activate α1-Adrenergic Cardiovascular Receptors

被引：30

作者：

Haase, Nadine ^{[1
]}

Herse, Florian ^{[1
]}

Spallek, Bastian ^{[1
]}

Haase, Hannelore ^{[2
]}

Morano, Ingo ^{[2
]}

Qadri, Fatimunnisa ^{[1
]}

Szijarto, Istvan A. ^{[1
]}

Rohm, Ilonka ^{[4
]}

Yilmaz, Atilla ^{[4
]}

Warrington, Junie P. ^{[5
]}

Ryan, Michael J. ^{[5
]}

Gollasch, Maik ^{[1
]}

Mueller, Dominik N. ^{[1
]}

Dechend, Ralf ^{[1
,3
]}

Wallukat, Gerd ^{[1
]}

机构：

[1] Expt & Clin Res Ctr, D-13125 Berlin, Germany

[2] Max Delbrueck Ctr Mol Med, Berlin, Germany

[3] HELIOS Klin, Dept Cardiol & Nephrol, Berlin, Germany

[4] Jena Univ Hosp, Dept Cardiol, Jena, Germany

[5] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA

来源：

HYPERTENSION | 2013年 / 62卷 / 05期

关键词：

alpha 1-adrenergic receptor; Alzheimer disease; amyloid-; peptides; hypertension; signal transduction; vasoconstriction; MIDLIFE BLOOD-PRESSURE; ALZHEIMERS-DISEASE; BRAIN; CONFORMATIONS; VASOACTIVITY; RISK;

D O I：

10.1161/HYPERTENSIONAHA.113.01348

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Alzheimer disease features amyloid- (A) peptide deposition in brain and blood vessels and is associated with hypertension. A peptide can cause vasoconstriction and endothelial dysfunction. We observed that A peptides exert a chronotropic effect in neonatal cardiomyocytes, similar to (1)-adrenergic receptor autoantibodies that we described earlier. Recently, it was shown that (1)-adrenergic receptor could impair blood-brain flow. We hypothesized that A peptides might elicit a signal transduction pathway in vascular cells, induced by (1)-adrenergic receptor activation. A (25-35) and A (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 (1)-adrenergic receptor blockers (urapidil, 1.53 +/- 1.17 bpm; prazosin, 0.30 +/- 0.96 bpm). Both A peptides induced an intracellular calcium release in vascular smooth muscle cells. Chronotropic activity and calcium response elicited by A (25-35) were blocked with peptides corresponding to the first extracellular loop of the (1)-adrenergic receptor. We observed an induction of extracellular-regulated kinase 1/2 phosphorylation by A (25-35) in Chinese hamster ovary cells overexpressing (1)-adrenergic receptor, vascular smooth muscle cells, and cardiomyocytes. We generated an activation-state-sensitive (1)-adrenergic receptor antibody and visualized activation of the (1)-adrenergic receptor by A peptide. A (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 (1)-adrenergic receptor blockade. Our data are relevant to the association between Alzheimer disease and hypertension. They may explain impairment of vascular responses by A and could have therapeutic implications.

引用

页码：966 / 972

页数：7

共 31 条

[1] Hypertension Induces Brain β-Amyloid Accumulation, Cognitive Impairment, and Memory Deterioration Through Activation of Receptor for Advanced Glycation End Products in Brain Vasculature [J].