实验性心力衰竭后心脏肾素-血管紧张素系统的选择性及时间相关性激活：与心室功能和形态的关系

Selective and time related activation of the cardiac renin-angiotensin system after experimental heart failure: relation to ventricular function and morphology.

作者信息

Pinto Y M, de Smet B G, van Gilst W H, Scholtens E, Monnink S, de Graeff P A, Wesseling H

机构信息

Department of Clinical Pharmacology, University of Groningen, The Netherlands.

出版信息

Cardiovasc Res. 1993 Nov;27(11):1933-8. doi: 10.1093/cvr/27.11.1933.

DOI:10.1093/cvr/27.11.1933

PMID:8287399

Abstract

OBJECTIVE

The cardiac renin-angiotensin system is activated in experimental heart failure, but it is unknown at what stage of heart failure it becomes activated, and whether activation is related to ventricular dysfunction and dilatation. Changes in activity of cardiac, renal, and plasma angiotensin converting enzyme (ACE) were therefore examined at different stages of experimental heart failure, with simultaneous measurements of left ventricular pressure, systolic dP/dt, and inner ventricular radius.

METHODS

Heart failure was induced by experimental infarction in 17 normotensive male Wistar rats; 14 rats were sham operated. Rats were killed 3, 5, or 80 d after infarction. In an isolated heart perfusion, left ventricular pressure and systolic dP/dT were measured. ACE activity was determined in samples of the left and right cardiac ventricle, kidney, and plasma. Radius of the ventricular cavity was planimetrically determined in transverse sections of the left ventricle.

RESULTS

At the different stages both left ventricular pressure and systolic dP/dT progressively decreased and inner radius of the left ventricle increased in all heart failure groups. ACE activity in the left ventricle increased significantly in all heart failure groups and correlated inversely with left ventricular pressure (R = -0.81; p < 0.001) and dP/dt (R = -0.85; p < 0.001). ACE activity in the kidney was only increased 80 d after the induction of heart failure [17(SEM 1) v 11.2(0.5) nM His-Leu generated per min.mg-1, p < 0.01], while plasma ACE activity was not increased in any heart failure group.

CONCLUSIONS

Cardiac ACE is activated in the early stage after induction of heart failure and is related to the amount of dysfunction. ACE in the kidney is activated only in the chronic stage. The cardiac renin-angiotensin system therefore already appears to be an important neurohumoral adjustment in the early stage of heart failure and is thereby a suitable target for early intervention by ACE inhibitors.

摘要

目的

心脏肾素 - 血管紧张素系统在实验性心力衰竭中被激活，但尚不清楚该系统在心力衰竭的哪个阶段被激活，以及其激活是否与心室功能障碍和扩张有关。因此，在实验性心力衰竭的不同阶段，检测了心脏、肾脏和血浆中血管紧张素转换酶（ACE）的活性变化，同时测量了左心室压力、收缩期dP/dt和心室内径。

方法

通过实验性梗死诱导17只血压正常的雄性Wistar大鼠发生心力衰竭；14只大鼠接受假手术。在梗死后3、5或80天处死大鼠。在离体心脏灌注中，测量左心室压力和收缩期dP/dT。测定左、右心室、肾脏和血浆样本中的ACE活性。通过左心室横切面的平面测量法确定心室腔半径。

结果

在所有心力衰竭组中，不同阶段左心室压力和收缩期dP/dT均逐渐降低，左心室内径增加。所有心力衰竭组左心室中的ACE活性均显著增加，且与左心室压力呈负相关（R = -0.81；p < 0.001）以及与dP/dt呈负相关（R = -0.85；p < 0.001）。仅在心力衰竭诱导80天后肾脏中的ACE活性增加[每分钟每毫克产生17（标准误1）对11.2（0.5）nM组氨酸 - 亮氨酸，p < 0.01]，而在任何心力衰竭组中血浆ACE活性均未增加。