Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure.
Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure.
复制标题
在心力衰竭大鼠模型中，直接血管紧张素 II 阻断与转化酶抑制相比的血流动力学效应。
DOI：
10.1093/ajh/4.4.334s
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发表时间：
1991
影响因子：
3.2
通讯作者：
Morkin,E
中科院分区：
文献类型：
--
作者：
Raya,TE;Fonken,SJ;Lee,RW;Daugherty,S;Goldman,S;Wong,PC;Timmermans,PB;Morkin,E
本研究的目的是在心力衰竭大鼠模型中比较Captopril抑制转化酶与DuP 753直接阻断血管紧张素II（AII）的慢性作用。用Captopril（2g/L，N = 9）在它们的饮用水中或用DuP 753（40 mg/kg/天，通过胃管饲法，持续两周，N = 10）或安慰剂（N = 9）治疗患有梗塞后慢性心力衰竭的大鼠2周。在这个剂量下，DuP 753使长期治疗的正常和心力衰竭大鼠的对数剂量-升压反应曲线向右平行移动两个数量级。在心力衰竭大鼠中，DuP 753和Captopril使左心室舒张末期压从26.7 ± 1.5降至14.2 ± 3.0（P < .01）和15.8 ± 2.2 mm Hg左室舒张末期容积指数由2.71 ± 0.10降至2.03 ± 0.17（P <0.05静脉顺应性分别从2.27 ± 0.06增加到2.80 ± 0.18（P <0.05）和3.02 ± 0.21 mL/mm Hg/kg（P <0.01）。左心室重量/体重比、平均主动脉压、心率或右心房压无显著变化。总血量有下降趋势，但不显著，分别从65.8 ± 1.1 mL/kg降至59.4 ± 3.0 mL/kg和64.9 ± 3.9 mL/kg。因此，在心肌梗死后心力衰竭大鼠中，用DuP 753直接阻断AII或用Captopril抑制转化酶可产生相似的血流动力学变化。美国高血压杂志1991;4：334 S-340 S
The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with Captopril to direct blockade of angiotensin II (AII) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either Captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose-pressor response curve to AII parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and Captopril reduced left ventricular end-diastolic pressure from 26.7 ± 1.5 to 14.2 ± 3.0 (P < .01) and 15.8 ± 2.2 mm Hg (P < .05), respectively, left ventricular end-diastolic volume index from 2.71 ± 0.10 to 2.03 ± 0.17 (P < .05) and 2.18 ± 0.15 (P < .05), respectively; venous compliance increased from 2.27 ± 0.06 to 2.80 ± 0.18 (P < .05) and 3.02 ± 0.21 mL/mm Hg/kg (P < .01), respectively. There were no significant changes in left ventricular weight/body weight ratio, mean aortic pressure, heart rate, or right atrial pressure. There was a trend, but not significant, for a reduction in total blood volume from 65.8 ± 1.1 to 59.4 ± 3.0 and 64.9 ± 3.9 mL/kg, respectively. Thus, direct blockade of AII with DuP 753 or with converting enzyme inhibition with Captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction. Am J Hypertens 1991;4:334S-340S