Inada T, Fujiwara H, Hasegawa K, Araki M, Yamauchi-Kohno R, Yabana H, Fujiwara T, Tanaka M, Sasayama S
Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, Japan.
J Am Coll Cardiol. 1999 Feb;33(2):565-71. doi: 10.1016/s0735-1097(98)00564-6.
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).
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.
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.
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.
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.
本研究旨在探讨内源性内皮素-1（ET-1）在Bio 14.6叙利亚心肌病仓鼠（Bio）心肌生长中的作用。
虽然ET-1作为一种促生长肽，与继发性心肌肥厚的发生有关，但内源性ET-1在原发性心肌病心脏生长中的作用尚不清楚。
我们通过特异性夹心酶联免疫吸附测定法测量左心室ET-1水平。此外，我们研究了ET A型受体特异性拮抗剂T0201的长期作用。
与年龄匹配的对照F1B仓鼠（F1B）相比，Bio仓鼠在20周时左心室ET-1水平高1.8倍（p < 0.0005），在35周时高6.4倍（p < 0.0001）。Bio仓鼠肺中的ET-1水平在35周时仅升高1.3倍。免疫组织化学显示ET-1主要定位于心肌细胞。T0201治疗显著降低了Bio仓鼠的心重/体重比，但不影响F1B仓鼠的心重/体重比。组织学上，T0201将Bio仓鼠的心肌细胞直径降低到与F1B仓鼠相似的水平。然而，T0201不影响Bio或F1B仓鼠的纤维化程度。
心肌病仓鼠心脏中的ET-1水平以阶段依赖性和器官特异性方式升高。虽然心肌细胞变性和随后的替代性纤维化不需要ET-1途径，但在该动物模型中，心脏中ET-1合成的加速可能有助于剩余心肌细胞的病理性生长。
