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肥厚型心肌病叙利亚仓鼠心室肌细胞对血管紧张素II的反应性降低

Depressed responsiveness to angiotensin II in ventricular myocytes of hypertrophic cardiomyopathic Syrian hamster.

作者信息

Yamashita T, Nakaya H, Tohse N, Kusaka M, Uemura H, Sakuma I, Yasuda H, Kanno M, Kitabatake A

机构信息

Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.

出版信息

J Mol Cell Cardiol. 1994 Nov;26(11):1429-38. doi: 10.1006/jmcc.1994.1162.

DOI:10.1006/jmcc.1994.1162
PMID:7897667
Abstract

Electromechanical responsiveness to angiotensin II (Ang II) receptor stimulation in ventricular myocardium and myocytes of hypertrophic cardiomyopathic Syrian hamsters (BIO 14.6) was examined and compared with that in preparations of normal hamsters (F1B) using conventional microelectrode and patch clamp techniques. Action potential duration (APD) and developed tension (DT) corrected for the cross-sectional area of the papillary muscles of 14-20 week-old BIO 14.6 hamsters were significantly smaller than those in preparations of age-matched normal hamsters. An Ang II (1 microM)-induced increase in DT in BIO 14.6 papillary muscles (24.7 +/- 11.0%) was significantly smaller than that in F1B papillary muscles (53.8 +/- 8.5%), which was associated with a smaller increase in APD in BIO 14.6 papillary muscles. In ventricular myocytes of both BIO 14.6 and F1B hamsters. Ang II increased the calcium current (ICa) following a transient decrease in ICa. However, the magnitude of the Ang II-induced increase in ICa in BIO 14.6 myocytes (35.5 +/- 7.5%) was significantly smaller than that in F1B myocytes (86.0 +/- 19.7%), suggesting a causal relationship between ICa and mechanical response to Ang II in these hamsters. The depressed responsiveness to Ang II receptor stimulation in hypertrophic cardiomyopathic hamster is in a marked contrast with the enhanced responsiveness to alpha 1-adrenergic stimulation, which was demonstrated by previous studies, and may be one of adaptational changes to the activated renin-angiotensin system in the cardiomyopathy.

摘要

利用传统微电极和膜片钳技术,检测并比较了肥厚型心肌病叙利亚仓鼠(BIO 14.6)心室心肌和心肌细胞对血管紧张素II(Ang II)受体刺激的机电反应,并与正常仓鼠(F1B)标本进行了对比。14 - 20周龄BIO 14.6仓鼠乳头肌动作电位时程(APD)和舒张期张力(DT)经乳头肌横截面积校正后,显著小于年龄匹配的正常仓鼠标本。BIO 14.6乳头肌中,Ang II(1微摩尔)诱导的DT增加(24.7±11.0%)显著小于F1B乳头肌(53.8±8.5%),这与BIO 14.6乳头肌中APD增加较小有关。在BIO 14.6和F1B仓鼠的心室肌细胞中,Ang II在短暂降低钙电流(ICa)后增加了ICa。然而,BIO 14.6心肌细胞中Ang II诱导的ICa增加幅度(35.5±7.5%)显著小于F1B心肌细胞(86.0±19.7%),提示这些仓鼠中ICa与对Ang II的机械反应之间存在因果关系。肥厚型心肌病仓鼠对Ang II受体刺激反应性降低,与先前研究所证明的对α1 - 肾上腺素能刺激反应性增强形成显著对比,可能是心肌病中对激活的肾素 - 血管紧张素系统的适应性变化之一。

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