Altered expression of isoforms of myosin heavy chain mRNA in the failing rat heart is ameliorated by chronic treatment with an endothelin receptor antagonist.
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.
Sakai
S
S
Department of Internal Medicine, University of Tsukuba, Japan.
Miyauchi
T
T
Kobayashi
T
T
Yamaguchi
I
I
Goto
K
K
Sugishita
Y
Y
D000818:Animals; D002908:Chronic Disease; D065128:Endothelin Receptor Antagonists; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000201:enzymology*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D009218:Myosins / Q000096:biosynthesis*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats
D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D018995:Myosin Heavy Chains; D009218:Myosins; C072247:cyclo(Trp-Asp-Pro-Val-Leu)