Center for Experimental Medicine, Institute for Clinical and Experimental Medicine.
Department of Cardiology, University Hospital Motol and 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
J Hypertens. 2023 Jan 1;41(1):99-114. doi: 10.1097/HJH.0000000000003307. Epub 2022 Oct 7.
Evaluation of the effect of endothelin type A (ET A ) receptor blockade on the course of volume-overload heart failure in rats with angiotensin II-dependent hypertension.
Ren-2 renin transgenic rats (TGR) were used as a model of hypertension. Heart failure was induced by creating an aorto-caval fistula (ACF). Selective ET A receptor blockade was achieved by atrasentan. For comparison, other rat groups received trandolapril, an angiotensin-converting enzyme inhibitor (ACEi). Animals first underwent ACF creation and 2 weeks later the treatment with atrasentan or trandolapril, alone or combined, was applied; the follow-up period was 20 weeks.
Eighteen days after creating ACF, untreated TGR began to die, and none was alive by day 79. Both atrasentan and trandolapril treatment improved the survival rate, ultimately to 56% (18 of 31 animals) and 69% (22 of 32 animals), respectively. Combined ACEi and ET A receptor blockade improved the final survival rate to 52% (17 of 33 animals). The effects of the three treatment regimens on the survival rate did not significantly differ. All three treatment regimens suppressed the development of cardiac hypertrophy and lung congestion, decreased left ventricle (LV) end-diastolic volume and LV end-diastolic pressure, and improved LV systolic contractility in ACF TGR as compared with their untreated counterparts.
The treatment with ET A receptor antagonist delays the onset of decompensation of volume-overload heart failure and improves the survival rate in hypertensive TGR with ACF-induced heart failure. However, the addition of ET A receptor blockade did not enhance the beneficial effects beyond those obtained with standard treatment with ACEi alone.
评估内皮素 A（ET A ）受体阻断对血管紧张素 II 依赖性高血压大鼠容量超负荷性心力衰竭进程的影响。
使用 Ren-2 血管紧张素原转基因大鼠（TGR）作为高血压模型。通过创建腔静脉-主动脉瘘（ACF）来诱导心力衰竭。通过阿曲生坦实现选择性 ET A 受体阻断。为了进行比较，其他大鼠组接受了血管紧张素转换酶抑制剂（ACEi）特拉唑嗪。动物首先进行 ACF 造瘘，2 周后单独或联合应用阿曲生坦或特拉唑嗪进行治疗；随访期为 20 周。
ACF 造瘘后 18 天，未治疗的 TGR 开始死亡，到第 79 天无一只存活。阿曲生坦和特拉唑嗪治疗均提高了生存率，最终分别达到 56%（31 只动物中的 18 只）和 69%（32 只动物中的 22 只）。联合应用 ACEi 和 ET A 受体阻断将最终的生存率提高至 52%（33 只动物中的 17 只）。三种治疗方案对生存率的影响无显著差异。与未治疗的对照组相比，三种治疗方案均抑制了心脏肥大和肺水肿的发展，降低了左心室（LV）舒张末期容积和 LV 舒张末期压力，并改善了 ACF TGR 的 LV 收缩功能。
ET A 受体拮抗剂的治疗延迟了容量超负荷性心力衰竭失代偿的发生，并提高了高血压 ACF 诱导心力衰竭 TGR 的生存率。然而，与单独标准 ACEi 治疗相比，ET A 受体阻断的添加并未增强其有益效果。
