© 2002 European Society of Cardiology
Altered calcium transient and development of hypertrophy in β2-adrenoceptor overexpressing mice with and without pressure overload
a Medizinische Klinik II, Universitätsklinikum Luebeck Ratzeburger Allee 160, 23538 Luebeck, Germany
b Baker Medical Research Institute Melbourne, Australia
* Corresponding author. Tel.: +49-451-500-2402; fax: +49-451-500-6279 E-mail address: katlab{at}medinf.mu-luebeck.de
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Abstract |
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Transgenic (TG) mice with cardiac specific 200-fold overexpression of β2-adrenoceptors (β2-AR) have a facilitated development of heart failure following thoracic aortic constriction (TAC). We have studied the alterations of intracellular Ca2+ transients and myocyte size in wild-type (WT) and TG mice after TAC. Cardiomyocytes were isolated from mice 9 weeks after TAC or sham operation, and incubated with Fura 2/AM. The Ca2+ transients were determined by Spex dual wavelength Spectrometer during electrical stimulation. The cell size was also determined planimetrically. Cells of sham operated TG mice displayed higher systolic Ca2+ amplitude than respective WT group (
F340/F380 ratio: 1.05±0.08 vs. 0.63±0.05; P<0.01), a finding in keeping with enhanced ventricular contractility in the TG mice. However, hypertrophied and failing myocytes of TG animals showed a fall in Ca2+ transients from sham-operated control levels and there was no difference between TG and WT groups following TAC. In sham-operated groups, the cell size of TG mice was significantly bigger than in WT animals (3212±139 vs. 2605±162 µm2; P<0.05). The cell size increased to a similar extent in both groups after TAC (4715±216 vs. 5027±365 µm2, P=n.s.). In summary, hypertrophy of cardiomyocytes was present in β2-AR TG mice under baseline conditions. A further hypertrophy occurred during pressure overload to an extent similar to that in WT animals. However, the increased intracellular Ca2+ transient, seen in sham-operated TG mice, was no longer detectable following development of severe hypertrophy and heart failure. These findings provide explanation on the lack of hemodynamic benefit in β2-AR TG mice subjected to pressure overload.
Key Words: Intracellular calcium • β2-adrenoceptor • Transgenic mice • Hypertrophy • Heart failure • Pressure overload
Received July 26, 2002; Revised August 16, 2002; Accepted November 11, 2002
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