Upregulated expression of cardiac endothelin-1 participates in myocardial cell growth in Bio14.6 Syrian cardiomyopathic hamsters.
OBJECTIVE
The purpose of this study is to investigate the role of endogenous endothelin-1 (ET-1) in myocardial growth in Bio 14.6 Syrian cardiomyopathic hamsters (Bio).


BACKGROUND
While ET-1, as a growth-promoting peptide, has been implicated in the development of secondary cardiac hypertrophy, the role of endogenous ET-1 in cardiac growth in primary myocardial disease is unknown.


METHODS
We measured left ventricular ET-1 levels by a specific sandwich enzyme-linked immunosorbent assay. Furthermore, we examined the chronic effect of T0201, an ET type A receptor-specific antagonist.


RESULTS
The ET-1 levels in the left ventricles were 1.8-fold higher (p < 0.0005) at 20 weeks and 6.4-fold higher (p < 0.0001) at 35 weeks in the Bio compared to age-matched control F1B hamsters (F1B). The Bio ET-1 levels in the lungs exhibited an only 1.3-fold elevation at 35 weeks. Immunohistochemistry demonstrated the localization of ET-1 mainly in the cardiac myocytes. The treatment with T0201 significantly reduced the heart weight/body weight ratio in the Bio, but did not affect the heart weight/body weight ratio in the F1B. Histologically, T0201 reduced the myocyte diameter of Bio to a level similar with that of F1B. However, T0201 did not affect the extent of fibrosis in Bio or F1B.


CONCLUSIONS
The ET-1 level in the heart of cardiomyopathic hamsters increases in stage-dependent and organ-specific manners. Though myocyte degeneration and subsequent replacement fibrosis do not require an ET-1 pathway, the accelerated synthesis of ET-1 in the heart may contribute to the pathological growth of remaining myocytes in this animal model.
Inada
T
T
Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, Japan.
Fujiwara
H
H
Hasegawa
K
K
Araki
M
M
Yamauchi-Kohno
R
R
Yabana
H
H
Fujiwara
T
T
Tanaka
M
M
Sasayama
S
S
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D006224:Cricetinae; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D011743:Pyrimidines / Q000494:pharmacology; D011897:Random Allocation; D017466:Receptors, Endothelin / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation