Endothelin-1 and angiotensin II receptors in cells from rat hypertrophied heart - Receptor regulation and intracellular Ca2+ modulation
Endothelin-1 and angiotensin II receptors in cells from rat hypertrophied heart - Receptor regulation and intracellular Ca2+ modulation
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DOI：
10.1161/01.res.78.2.302
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发表时间：
1996-02-01
影响因子：
20.1
通讯作者：
Thibault, G
中科院分区：
文献类型：
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作者：
Fareh, J;Touyz, RM;Thibault, G
本研究探讨了内皮素-1（ET-1）和血管紧张素Ⅱ（Ang Ⅱ）受体在大鼠容量超负荷性心肌肥厚中的细胞定位和调节，以及ET-1和Ang Ⅱ对心肌[Ca ~（2+）]（i）的影响。采用放射性配体结合分析和Fura 2方法测定了4周下腔静脉分流大鼠心脏分离的心室心肌细胞和成纤维细胞的[Ca 2 +]（i）。在肥厚的心肌，ET-1和血管紧张素II浓度不变，在心室。心室ET-1受体具有细胞特异性分布：心肌细胞中>90%的ET受体为ET（A）亚型，而成纤维细胞中ET（A）和ET（B）亚型的比例几乎相等。在肥厚心肌的两种心室细胞类型中，ET-1受体密度、亲和力和ET-1诱导的[Ca 2 +]（i）与对照组无显著差异。血管紧张素II特异性结合是非常低的离体心室心肌细胞，表明在控制条件下很少的受体。然而，浓度>10（-8）mol/L的Ang II诱导的[Ca ~（2+）]（i）反应可检测到，并且在肥大的心肌细胞中显著更高。成纤维细胞上的Ang II受体密度（仅AT（1））显著降低（42 970+/-3330对对照细胞的73 870+/-7940位点/细胞，P
This study investigates the cellular localization and regulation of endothelin-l (ET-1) and angiotensin II (Ang II) receptors and the effects of ET-1 and Ang II on [Ca2+](i) in cardiac hypertrophy due to volume overload in the rat. Radioligand binding assays and [Ca2+](i) measurements by fura 2 methodology were performed on isolated ventricular cardiomyocytes and fibroblasts from the heart of rats with a 4-week aortocaval shunt. In the hypertrophied myocardium, ET-1 and Ang II concentrations were unchanged in ventricles. Ventricular ET-1 receptors had a cell-specific distribution: >90% of ET receptors in cardiomyocytes are of the ET(A) subtype, whereas fibroblasts had a nearly equal proportion of the ET(A) and ET(B) subtypes. ET-1 receptor densities, affinities, and ET-1-induced [Ca2+](i) were not significantly different from control in both Ventricular cell types from hypertrophied myocardium. Ang II specific binding was very low on isolated ventricular cardiomyocytes, suggesting few receptors in control conditions. However, [Ca2+](i) responses induced by Ang II at concentrations >10(-8) mol/L were detectable and were significantly higher in hypertrophied cardiomyocytes. Ang II receptor density (exclusively AT(1)) on fibroblasts was significantly reduced (42 970+/-3330 versus 73 870+/-7940 sites per cell for control cells, P