Alterations in angiotensin II receptor mediated signal transduction shortly after coronary artery constriction in the rat.
Alterations in angiotensin II receptor mediated signal transduction shortly after coronary artery constriction in the rat.
复制标题
大鼠冠状动脉收缩后不久血管紧张素 II 受体介导的信号转导发生变化。
DOI：
10.1093/cvr/28.10.1564
复制
发表时间：
1994
影响因子：
10.8
通讯作者：
Anversa,P
中科院分区：
文献类型：
--
作者：
Huang,H;Li,P;Hamby,CV;Reiss,K;Meggs,LG;Anversa,P
目的：探讨冠状动脉缩窄对冠状动脉狭窄术后1周心肌细胞血管紧张素II受体密度及受体偶联效应的影响。方法：建立大鼠冠状动脉狭窄模型，采用酶法分离心肌细胞，进行放射性配基结合实验。此外，等张收缩表现，胞内钙瞬变。在血管紧张素II受体亚型拮抗剂氯沙坦存在和不存在的情况下，检测血管紧张素II刺激心肌细胞肌醇磷酸生成。结果：在记录左心衰和右心功能不全后，左室肌细胞血管紧张素II受体的表达和密度分别增加3.1倍和4.1倍。右室心肌细胞相应增加3.6倍和4.5倍。相反，调节蛋白Gqα在两个脑室中的数量没有改变。在最大刺激条件下，血管紧张素I1不增加左、右室肌细胞总肌醇磷酸的生成。然而，冠脉狭窄大鼠左室肌细胞形成肌醇磷酸的阈值降低。单细胞力学测定表明，血管紧张素I1刺激可明显改善双室肌细胞功能的抑制。结论：在这种全脑缺血模型中，心肌细胞上血管紧张素I1受体的上调可能是一种代偿机制，改善心肌细胞的收缩能力，以维持心室泵功能。心血管研究1994；28：1564-1573
Objective:The aim of the study was to determine the effect of coronary artery constriction on the density of angiotensin II receptors and on the effector responses coupled with these receptors on myocytes one week after surgical induction of coronary artery stenosis in rats.Methods: After induction of coronary artery stenosis and following the estimation of global cardiac performance, myocytes were enzymatically dissociated and radio- ligand binding studies were performed. In addition, the isotonic contractile performance, cytosolic calcium transients. and angiotensin II stimulated inositol phosphate generation in myocytes were measured in the presence and absence of the angiotensin II receptor subtype antagonist losartan. Results: After documenting left ventricular failure and right ventricular dysfunction, the expression and density of angiotensin II receptors in left ventricular niyocytes were evaluated and found to be increased 3.1 -fold and 4.1 -fold, respectively. Corresponding increases in right ventricular myocytes were 3.6-fold and 4.5-fold. In contrast, the quantity of the regulatory protein Gqαwas not altered in either ventricle. Angiotensin I1 did not increase the generation of total inositol phosphates in left and right ventricular myocytes at maximum stimulation. However, the threshold for the formation of inositol phosphates was lowered in left ventricular myocytes of coronary narrowed rats. Measurements of single cell mechanics indicated that angiotensin I1 stimulation markedly improved the depression in myocyte function biventricularly. This inotropic effect was coupled with the restoration of cytosolic calcium.Conclusions: The upregulation of angiotensin I1 receptors on myocytes in this model of global ischaemia may be a compensatory mechanism ameliorating myocyte contractility in an attempt to sustain Ventricular pump function.Cardiovascular Research1994;28:1564-1573