Inhibition of the Renin-Angiotensin System Abolishes the Proatherogenic Effect of Uremia in Apolipoprotein E-Deficient Mice

Abstract

Objective— Uremia accelerates atherosclerosis in apolipoprotein E-deficient (apoE ^−/− ) mice. We examined whether this effect may be preventable by pharmacological blockade of the renin-angiotensin system (RAS). Methods and Results— Uremia was induced in apoE ^−/− mice by 5/6 nephrectomy (NX). Treatment with the angiotensin converting enzyme inhibitor enalapril (2 or 12 mg/kg/d) from week 4 to 36 after NX reduced the aortic plaque area fraction from 0.23±0.02 (n=20) in untreated mice to 0.11±0.01 (n=21) and 0.08±0.01 (n=23), respectively ( P P P P Conclusion— The results suggest that inhibition of RAS abolishes the proatherogenic effect of uremia independent of its blood pressure-lowering effect, possibly because of antiinflammatory and antioxidative mechanisms.