Abstract: TH-PO379

Modulation of Oxidative Stress by Inhibition of Angiotensin II Type 1 Receptors in Cardiorenal Syndrome

Session Information

Category: Cell Biology

  • 201 Cell Signaling, Oxidative Stress

Author

  • Farahmand, Firoozeh, None, Richmond Heights, Missouri, United States
Background

Cardiorenal syndrome (CRS) has a complex pathophysiology that is still not completely understood. Oxidative stress is one of the key mediators of CRS. The aims of this study were to examine if an experimental model of CRS type 1 is associated with oxidative stress and whether blocking of the renin-angiotensin system (RAS) at the angiotensin II type 1 (AT1) receptor site is accompanied by changes in the oxidative stress parameters and attenuates CRS.

Methods

Rats were randomized into 4 groups: control, myocardial infarction (MI), MI group treated with losartan and control group treated with losartan. MI was induced by the ligation of the left coronary artery. At 4 weeks post-MI, animals were examined for hemodynamic function including left ventricle (LV) systolic pressure (LVSP), aortic systolic (AS)pressure, LV diastolic pressure, LV hypertrophy (LVH), and LV function.
Hearts and the kidneys were analyzed for antioxidant enzyme activities including superoxide dismutase, glutathione peroxidase, catalase and oxidative stress. After sacrificing the animals, the renal cortex and the heart were removed for histology.

Results

At 4 weeks post MI there was a significant drop in LVSP and ASP associated with increased renal and myocardial lipid peroxidation to 63%, and 57% respectively . In MI group there was a decerase in in antioxidants enzymes activities in the kidney including catalase (34%), glutathione peroxidase ( 43%) and superoxide dismutase (51%). In the MI+ Losartan group losartan improved hemodynamic function and decerase oxidative stress in the kidney to 59% compared with MI group.(p-value less than 0.05).

Conclusion


In CRS type 1 congestive heart failure and acute kidney injury (AKI) in rats after MI correlates with a decrease in antioxidant and increase in oxidative stress in the heart and the kidney. Inhibition of the RAS with losartan improves cardiac function and survival in MI rats as well as oxidative stress parameter in the kidney. This study suggest the beneficial effects of angiotensin II type 1 (AT1) receptor blocker in the treatent of CRS.