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 - PubMed (original) (raw)

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

Matej Durik et al. Int J Hypertens. 2012.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Comparison of heart weight/body weight ratios between the different treatments (a), variables of cardiac hypertrophy: myocyte, cross-sectional area (b), and myocyte density (c). (*P < 0.05, One way ANOVA, Dunnett's post hoc testing).

Figure 2

Figure 2

Effects of cAng 1–7 on left ventricular end-diastolic pressure and minimal pressure in both sham-operated rats and rats with myocardial infarction. (# P < 0.05_t_-test sham saline versus sham cAng-(1–7); *P < 0.05, One way ANOVA for MI groups, Dunnett's post hoc testing; $ P < 0.05 for linear trend for MI groups).

Figure 3

Figure 3

Endothelial-dependent dilator function of rat aorta to metacholine (a), after blockade of eNOS/NO signaling (b), and after combined blockade of eNOS/NO and EDHF vasodilator mechanisms (c). (*P < 0.05, GLM-RM).

Similar articles

Cited by

References

    1. Iusuf D, Henning RH, van Gilst WH, Roks AJM. Angiotensin-(1–7): pharmacological properties and pharmacotherapeutic perspectives. European Journal of Pharmacology. 2008;585(2-3):303–312. - PubMed
    1. Ferreira AJ, Santos RAS, Bradford CN, et al. Therapeutic implications of the vasoprotective axis of the renin-angiotensin system in cardiovascular diseases. Hypertension. 2010;55(2):207–213. - PMC - PubMed
    1. Santos RAS, Simoes e Silva AC, Maric C, et al. Angiotensin-(1–7) is an endogenous ligand for the G protein-coupled receptor Mas. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(14):8258–8263. - PMC - PubMed
    1. Loot AE, Roks AJM, Henning RH, et al. Angiotensin-(1–7) attenuates the development of heart failure after myocardial infarction in rats. Circulation. 2002;105(13):1548–1550. - PubMed
    1. Wang Y, Qian C, Roks AJM, et al. Circulating rather than cardiac angiotensin-(1–7) stimulates cardioprotection after myocardial infarction. Circulation. 2010;3(2):286–293. - PubMed

LinkOut - more resources