β 2 -Adrenergic Receptor Overexpression Exacerbates Development of Heart Failure After Aortic Stenosis
- 4 January 2000
- journal article
- other
- Published by Wolters Kluwer Health in Circulation
- Vol. 101 (1) , 71-77
- https://doi.org/10.1161/01.cir.101.1.71
Abstract
Background—β-Adrenergic signaling is downregulated in the failing heart, and the significance of such change remains unclear. Methods and Results—To address the role of β-adrenergic dysfunction in heart failure (HF), aortic stenosis (AS) was induced in wild-type (WT) and transgenic (TG) mice with cardiac targeted overexpression of β2-adrenergic receptors (ARs), and animals were studied 9 weeks later. The extents of increase in systolic arterial pressure (PPPPmax and heart rate were markedly higher in TG than WT mice (both Pmax was lower in both AS groups than in sham-operated controls, and this tended to be more pronounced in TG than WT mice (−32±5% versus −16±6%, P=0.059), although dP/dtmax remained higher in TG than WT groups (PConclusions—Elevated cardiac β-adrenergic activity by β2-AR overexpression leads to functional deterioration after pressure overload.Keywords
This publication has 21 references indexed in Scilit:
- Remodelling of Cardiac Extracellular Matrix duringβ-adrenergic Stimulation: Upregulation of SPARC in the Myocardium of Adult Rats,Journal of Molecular and Cellular Cardiology, 1998
- Selective Activation ofα1A-adrenergic Receptors in Neonatal Cardiac Myocytes is Sufficient to Cause Hypertrophy and Differential Regulation ofα1-adrenergic Receptor Subtype mRNAsJournal of Molecular and Cellular Cardiology, 1998
- Control of Myocardial Contractile Function by the Level of β-Adrenergic Receptor Kinase 1 in Gene-targeted MicePublished by Elsevier ,1998
- Expression of a β-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted miceProceedings of the National Academy of Sciences, 1998
- Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium.Journal of Clinical Investigation, 1997
- Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the β2-adrenoceptorNature, 1995
- Mineralocorticoids, hypertension, and cardiac fibrosis.Journal of Clinical Investigation, 1994
- Enhanced Myocardial Function in Transgenic Mice Overexpressing the β 2 -Adrenergic ReceptorScience, 1994
- Reduced beta 1 receptor messenger RNA abundance in the failing human heart.Journal of Clinical Investigation, 1993
- Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy. Interaction between hemodynamic and thyroid hormone-induced signals.Journal of Clinical Investigation, 1987