We have reported that the production of
endothelin (ET)-1 is markedly increased in the failing heart of rats with chronic
heart failure (CHF) and that the long-term (3-month) treatment with the ETA receptor antagonist
BQ-123 markedly ameliorated the long-term survival and hemodynamic parameters in rats with CHF. In this study we investigated whether this
therapy affects the alteration of the
mRNA expression of
cardiac myosin heavy chain (MHC)
isoforms in the hearts of rats with CHF. The change from alpha-MHC to beta-MHC is regarded as a molecular marker for
heart failure. The expression of beta-MHC
mRNA was dominant in the left ventricle (LV) of CHF rats treated with saline, whereas that of alpha-MHC was dominant in the LV of
sham-operated rats treated with saline. Therefore, in the failing rat heart, a change from alpha-MHC to beta-MHC occurred. In the LV of CHF rats treated with
BQ-123, this treatment effectively prevents the switching of MHC
isoforms. These findings suggest that long-term
BQ-123 treatment inhibits the change in MHC
isoforms and suggest that this treatment ameliorates
heart failure in CHF rats at the molecular level.