Angiotensin II-induced sudden arrhythmic death and electrical remodeling
Angiotensin II-induced sudden arrhythmic death and electrical remodeling
复制标题
DOI：
10.1152/ajpheart.01400.2006
复制
发表时间：
2007-08-01
影响因子：
4.8
通讯作者：
Schirdewan, Alexander
中科院分区：
文献类型：
--
作者：
Fischer, Robert;Dechend, Ralf;Schirdewan, Alexander
携带人肾素和血管紧张素原基因 (dTGR) 的大鼠具有血管紧张素 (ANG) II/高血压引起的心脏损伤，并在第 7 周和第 8 周之间突然死亡。我们通过心电图 (ECG) 遥测观察到，室性心动过速 (VT) 是这些动物中常见的终末事件。我们的目的是研究电气改造。我们在第 5 周和第 7 周使用心电图遥测、无创心脏磁场测绘 (CMFM)，并在第 7 周进行体内编程电刺激。我们还研究了氯沙坦 (Los; 30 mg . kg(-1) . day(-1)) 是否会预防电重构。与 Sprague-Dawley (SD) 对照相比，dTGR 中心脏肥大和收缩压逐渐升高。到第 5 周时，与 SD 大鼠相比，未经治疗的 dTGR 已显示出血管周围和间质纤维化、结缔组织生长因子表达和单核细胞浸润增加，且差异随着时间的推移而进展。与Los处理的dTGR和SD相比，dTGR中钾通道亚基Kv4.3和间隙连接蛋白连接蛋白43的左心室mRNA表达显着降低。 CMFM 显示去极化和复极化时间延长且不均匀。洛斯改善了所有的干扰。 VT 可在 88% 的 dTGR 中诱导，但仅在 33% 的 Los 处理的 dTGR 中诱导，并且在 SD 中不能诱导。未经处理的 dTGR 显示出电重塑，并可能死于 VT。 Los治疗可减少心肌重塑和心律失常的倾向。 ANG II 靶器官损伤诱发 VT。
Rats harboring the human renin and angiotensinogen genes ( dTGR) feature angiotensin ( ANG) II/ hypertension-induced cardiac damage and die suddenly between wk 7 and 8. We observed by electrocardiogram ( ECG) telemetry that ventricular tachycardia ( VT) is a common terminal event in these animals. Our aim was to investigate electrical remodeling. We used ECG telemetry, noninvasive cardiac magnetic field mapping ( CMFM) at wk 5 and 7, and performed in vivo programmed electrical stimulation at wk 7. We also investigated whether or not losartan ( Los; 30 mg . kg(-1) . day(-1)) would prevent electrical remodeling. Cardiac hypertrophy and systolic blood pressure progressively increased in dTGR compared with Sprague-Dawley ( SD) controls. Already by wk 5, untreated dTGR showed increased perivascular and interstitial fibrosis, connective tissue growth factor expression, and monocyte infiltration compared with SD rats, differences that progressed through time. Left-ventricular mRNA expression of potassium channel subunit Kv4.3 and gap-junction protein connexin 43 were significantly reduced in dTGR compared with Los-treated dTGR and SD. CMFM showed that depolarization and repolarization were prolonged and inhomogeneous. Los ameliorated all disturbances. VT could be induced in 88% of dTGR but only in 33% of Los-treated dTGR and could not be induced in SD. Untreated dTGR show electrical remodeling and probably die from VT. Los treatment reduces myocardial remodeling and predisposition to arrhythmias. ANG II target organ damage induces VT.