科研之友
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摘要
Transgenic (TG) mice with cardiac specific 200-fold overexpression of beta(2)-adrenoceptors (beta(2)-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 (DeltaF(340)/F-380 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 bioger than in WT animals (3212 +/- 139 vs. 2605 +/- 162 mum(2) P<0.05). The cell size increased to a similar extent in both groups after TAC (4715 +/- 216 vs. 5027 +/- 365 mum(2). P=n.s.). In summary, hypertrophy of cardiomyocytes was present in beta(2)-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 hernodynarnic benefit in beta(2)-AR TG mice subjected to pressure overload.
- 出版日期2003-3
