Altered myocardial thin-filament function in the failing Dahl salt-sensitive rat heart - Amelioration by endothelin blockade

Article

关键词: PROTEIN-KINASE-C;    CARDIAC TROPONIN-I;    COMPENSATORY HYPERTROPHY;    VENTRICULAR MYOCARDIUM;    TRANSITION;    FAILURE;    PHOSPHORYLATION;    ISOZYMES;    AFFINITY;   

DOI  :  10.1161/01.CIR.0000046267.16901.E9

来源: SCIE

【 摘 要 】

Background-Dahl salt-sensitive rats fed a high-salt diet develop compensated left ventricular hypertrophy followed by a transition to myocardial failure. We previously reported an increase in a troponin T isoform (TnT(3)) and a decrease in TnT phosphorylation in failing Dahl salt-sensitive rat hearts compared with low-salt controls. The present study was undertaken to determine whether the thin filament plays a role in depression of the contractile machinery in this model. Methods and Results-Native thin filaments (NTFs) were isolated intact from rats with compensated left ventricular hypertrophy and failing hearts and compared with age-matched controls. NTF velocity was measured as a function of free calcium in the in vitro motility assay. Maximal velocity was similar in all groups. However, NTFs from failing hearts demonstrated a reduction in calcium sensitivity compared with controls, as reflected in the pCa(50) (5.88 +/- 0.05 versus 6.22 +/- 0.05, respectively, P<0.001). No difference in thin-filament motility (pCa(50), V-max) was observed in rats with compensated left ventricular hypertrophy compared with controls. Protein kinase A treatment of NTFs from control and failing hearts had no effect on thin-filament calcium sensitivity. However, the endothelin receptor blocker bosentan prevented the reduction in thin-filament calcium sensitivity found in failing hearts. Conclusions-The thin filament is a key modulator of contractile performance in the transition to failure in the Dahl salt-sensitive rat model. The alteration in thin-filament function may be mediated by an endothelin-triggered pathway potentially affecting protein kinase C signaling.

【 授权许可】

Free