Abstract 11305: Protective Effects of Homoarginine on Cardiovascular Function in a Mouse Model of Chronic Kidney Disease

Abstract

Introduction: The level of homoarginine (hArg) in plasma correlates inversely with cardiovascular and renal disease. However, the cardioprotective mechanism of hArg in renal disease is currently unknown. In this study, we assessed hArg’s effects on cardiovascular function in mice with chronic kidney disease (CKD). Hypothesis: We have previously reported that hArg reduces fibrosis and helps preserve ejection fraction in a model of coronary artery disease. We now hypothesize that hArg supplementation will 1) decrease cardiac and renal fibrosis and inflammation in a model of CKD, 2) preserve cardiac geometry and function, 3) increase renal artery blood flow, and 4) increase survival. Methods: The mice used in this study had a mutation in the low density lipoprotein receptor on the C57BL/6 genetic background. Mice of both sexes (n=28) were fed a standard rodent diet supplemented with 0.1% (F) and 0.2% (M) adenine to induce CKD. Mice were randomly assigned to 14 μg/ml hArg (in drinking water) or placebo (PBO). Cardiac structure and function as well as renal blood flow were measured via high frequency ultrasound (Vevo 3100, VisualSonics). Results: LV geometry data of hArg treated male mice showed increased left ventricular (LV) mass (p<0.05) with normal LV internal diameter and increased LV wall thickness (p<0.01). In terms of cardiac function, ejection fraction (EF, p<0.05), fractional shortening (p<0.01), and cardiac output (p<0.01) were also increased in hArg treated male mice compared to placebo. No differences in renal blood flow were observed. Survival was not affected by hArg. Additionally, we observed decreased food consumption (p<0.01) and fecal output (p<0.001) in hArg treated mice with no difference in urine output compared with placebo. Conclusion: hArg treated male mice developed physiologic cardiac hypertrophy with preserved EF in the absence of LV dilation. Additionally, hArg affected the metabolic state of treated mice reflected in food consumption.