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 (TnT3) 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 pCa50 (5.88+/-0.05 versus 6.22+/-0.05, respectively, P<0.001). No difference in thin-filament motility (pCa50, 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.
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 (TnT3) 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 pCa50 (5.88+/-0.05 versus 6.22+/-0.05, respectively, P<0.001). No difference in thin-filament motility (pCa50, 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.
Authors: Rashad J Belin; Marius P Sumandea; Gail A Sievert; Laura A Harvey; David L Geenen; R John Solaro; Pieter P de Tombe Journal: Pflugers Arch Date: 2011-09-17 Impact factor: 3.657
Authors: M Louhelainen; E Vahtola; P Kaheinen; H Leskinen; S Merasto; V Kytö; P Finckenberg; W S Colucci; J Levijoki; P Pollesello; H Haikala; E M A Mervaala Journal: Br J Pharmacol Date: 2007-02-26 Impact factor: 8.739
Authors: Natalya Bodyak; Juan Carlos Ayus; Steven Achinger; Venkatesha Shivalingappa; Qingen Ke; Yee-Shiuan Chen; Debra L Rigor; Isaac Stillman; Hector Tamez; Paul E Kroeger; Ruth R Wu-Wong; S Ananth Karumanchi; Ravi Thadhani; Peter M Kang Journal: Proc Natl Acad Sci U S A Date: 2007-10-17 Impact factor: 11.205