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

Modulation of renin-angiotensin system (RAS) by angiotensin-(17) (Ang-(17)) is an attractive approach to combat the detrimental consequences of myocardial infarction (MI). However Ang-(17) has limited clinical potential due to its unfavorable pharmacokinetic profile. We investigated effects of a stabilized, thioether-bridged analogue of Ang-(17) called cyclic Ang-(17) 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-(17) 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-(17) treatment. MI increased heart weight and myocyte size, which was restored by cAng-(17) to sham levels. In addition, cAng-(17) lowered left ventricular end-diastolic pressure and improved endothelial function. The results suggest that cAng-(17) is a promising new agent in treatment of myocardial infarction and warrant further research.

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