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(Circulation. 2000;101:71.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
ß2-Adrenergic Receptor Overexpression Exacerbates Development of Heart Failure After Aortic Stenosis
From the Baker Medical Research Institute, Melbourne, Australia.
Correspondence to X.-J. Du, Baker Medical Research Institute, St Kilda Road Central, PO Box 6492, Melbourne 8008, Victoria, Australia. E-mail xiaojun.du{at}baker.edu.au
Background—ß-Adrenergic signaling is downregulated in the failing heart, and the significance of such change remains unclear.
Methods and Results—To address the role of ß-adrenergic dysfunction in heart failure (HF), aortic stenosis (AS) was induced in wild-type (WT) and transgenic (TG) mice with cardiac targeted overexpression of ß2-adrenergic receptors (ARs), and animals were studied 9 weeks later. The extents of increase in systolic arterial pressure (P<0.01 versus controls), left ventricular (LV) hypertrophy (TG, 94±6 to 175±7 mg; WT, 110±6 to 168±10 mg; both P<0.01), and expression of ANP mRNA were similar between TG and WT mice with AS. TG mice had higher incidences of premature death and critical illness due to heart failure (75% versus 23%), pleural effusion (81% versus 45%), and left atrial thrombosis (81% versus 36%, all P<0.05). A more extensive focal fibrosis was found in the hypertrophied LV of TG mice (P<0.05). These findings indicate a more severe LV dysfunction in TG mice. In sham-operated mice, LV dP/dtmax and heart rate were markedly higher in TG than WT mice (both P<0.01). dP/dtmax 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 (P<0.05).
Conclusions—Elevated cardiac ß-adrenergic activity by ß2-AR overexpression leads to functional deterioration after pressure overload.
Key Words: genetics • receptors, adrenergic, beta • hypertrophy • heart failure • pressure
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