Angiotensin-(1-7) attenuates the development of heart failure after myocardial infarction in rats

被引:269
作者
Loot, AE
Roks, AJM
Henning, RH
Tio, RA
Suurmeijer, AJH
Boomsma, F
van Gilst, WH
机构
[1] Univ Groningen, Dept Clin Pharmacol, Groningen, Netherlands
[2] Univ Groningen Hosp, Dept Cardiol, Groningen, Netherlands
[3] Univ Groningen Hosp, Dept Pathol, Groningen, Netherlands
[4] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands
关键词
angiotensin; heart failure; hemodynamics; myocardial infarction;
D O I
10.1161/01.CIR.0000013847.07035.B9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-The renin-angiotensin system (RAS) is a key player in the progression of heart failure. Angiotensin-(1-7) is thought to modulate the activity of the RAS. Furthermore, this peptide may play a part in the beneficial effects of angiotensin-converting enzyme inhibitors in cardiovascular disease. We assessed the effects of angiotensin-(1-7) tin the progression of heart failure. Methods and Results-Male Sprague-Dawley rats underwent either coronary legation or sham surgery. Two weeks after induction of myocardial infarction, intravenous infusion of angiotensin-(1-7) (24 mug/kg per hour) or saline was started by minipump. After 8 weeks of treatment, hemodynamic parameters were measured, endothelial function was assessed in isolated aortic rings, and plasma angiotensin-(1-7) levels were determined. Myocardial infarction resulted in a significant deterioration of left ventricular systolic and diastolic pressure, dP/dt, and coronary flow. Raising plasma levels 40-fold, angiotensin-(1-7) infusion attenuated this impairment to a nonsignificant level, markedly illustrated by a 40% reduction in left ventricular end-diastolic pressure. Furthermore, angiotensin-(1-7) completely preserved aortic endothelial function, whereas endothelium-dependent relaxation in aortas of saline-treated infarcted rats was significantly decreased. Conclusions-Angiotensin-(1-7) preserved cardiac function, coronary perfusion, and aortic endothelial function in a rat model fur heart failure.
引用
收藏
页码:1548 / 1550
页数:3
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