title: Altered calcium transient and development of hypertrophy in beta2-adrenoceptor overexpressing mice with and without pressure overload.
abstract: 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 microm(2); P<0.05). The cell size increased to a similar extent in both groups after TAC (4715+/-216 vs. 5027+/-365 microm(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 Ca(2+) 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 beta(2)-AR TG mice subjected to pressure overload.
authors.affiliation: Medizinische Klinik II, Universitätsklinikum Luebeck, Ratzeburger Allee 160, 23538, Luebeck, Germany. katlab@medinf.mu-luebeck.de
authors.forename: Bettina
authors.initials: B
authors.lastname: Schwarz
authors.forename: Elodie
authors.initials: E
authors.lastname: Percy
authors.forename: Xiao Ming
authors.initials: XM
authors.lastname: Gao
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Dart
authors.forename: Gert
authors.initials: G
authors.lastname: Richardt
authors.forename: Xiao Jun
authors.initials: XJ
authors.lastname: Du
mesh_terms: D000818:Animals; D000835:Animals, Wild; D020747:Calcium Channels, T-Type / Q000096:biosynthesis*; D006348:Cardiac Surgical Procedures; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D015994:Incidence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000473:pathology; D009657:North Carolina; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis*; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D017725:Ventricular Pressure / Q000502:physiology*
chemical_list: D020747:Calcium Channels, T-Type; D018343:Receptors, Adrenergic, beta-2