The effect of the thioether-bridged, stabilized Angiotensin-(1-7) analogue cyclic ang-(1-7) on cardiac remodeling and endothelial function in rats with myocardial infarction.
The effect of the thioether-bridged, stabilized Angiotensin-(1-7) analogue cyclic ang-(1-7) on cardiac remodeling and endothelial function in rats with myocardial infarction.
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DOI:
10.1155/2012/536426
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发表时间:
2012
影响因子:
1.9
通讯作者:
Roks AJ
中科院分区:
文献类型:
--
作者:
Durik M;van Veghel R;Kuipers A;Rink R;Haas Jimoh Akanbi M;Moll G;Danser AH;Roks AJ
Modulation of renin-angiotensin system (RAS) by angiotensin-(1–7) (Ang-(1–7)) is an attractive approach to combat the detrimental consequences of myocardial infarction (MI). However Ang-(1–7) has limited clinical potential due to its unfavorable pharmacokinetic profile. We investigated effects of a stabilized, thioether-bridged analogue of Ang-(1–7) called cyclic Ang-(1–7) in rat model of myocardial infarction. Rats underwent coronary ligation or sham surgery. Two weeks thereafter infusion with 0.24 or 2.4 μg/kg/h cAng-(1–7) or saline was started for 8 weeks. Thereafter, cardiac morphometric and hemodynamic variables as wells as aortic endothelial function were measured. The average infarct size was 13.8% and was not changed by cAng-(1–7) treatment. MI increased heart weight and myocyte size, which was restored by cAng-(1–7) to sham levels. In addition, cAng-(1–7) lowered left ventricular end-diastolic pressure and improved endothelial function. The results suggest that cAng-(1–7) is a promising new agent in treatment of myocardial infarction and warrant further research.