Abstract P174: Determining The Effect Of Diet And Short-term Voluntary Exercise On Renal Function And RAS mRNA Expression In Male C57Bl/6 Mice: A Pilot Study

Abstract

Poor dietary quality and exercise are key risk factors for kidney and cardiovascular diseases. Dietary quality is not considered in most preclinical animal studies and has likely hindered overall progress in biomedical research. We developed a novel diet to model the nutritional inadequacies of Americans and our data suggest poor dietary quality influences kidney function. Therefore, the goal of the current study is to determine how diet and exercise impact kidney and cardiovascular health in mice. Male C57Bl/6 mice were assigned to 1 of 3 diets: chow, synthetic AIN93G, or our novel Americanized diet (AD). Mice were assigned to exercise or control groups, with exercise being free access to an exercise wheel for 16 hours 3 times a week. After 4 weeks, systolic blood pressure (SBP) and renal blood flow (RBF) were quantified in a subset of each group. Renal mRNA expression of RAS genes was determined by RT-PCR in the remaining animals. Data were analyzed using General Linear Model Procedures in SPSS, with significance determined at P <0.05 and a tendency indicated at P <0.1. Neither diet ( P =0.6) nor exercise ( P= 0.5) significantly influenced SBP or RBF, however, a significant diet*exercise interaction occurred ( P =0.03). AIN-fed mice with exercise had a significantly lower (94±8 mmHg, p=0.009) blood pressure as compared to the AIN control group (116±4 mmHg). Similarly, exercise also tended ( P =0.09) to reduce RBF in mice fed AIN. Exercise, regardless of diet, resulted in a doubling (p=0.03) in renal angiotensinogen expression as compared to control mice. This effect was most apparent in mice fed chow. Diet also mediated the significant effect of exercise on renal Mme expression ( P =0.04), with exercise lowering Mme expression in mice fed AIN and AD (50% reduction) and increasing its expression (3-times greater) in mice fed chow. A similar trend was observed with Agtr1a ( P =0.07). Regardless of diet, exercise also tended to upregulate Ace1 (p=0.054) compared to control mice. Results of this pilot study suggest that diet significantly influences the physiological response to exercise, particularly renal physiology and the control of blood pressure. Additional studies are needed to confirm these preliminary results and identify the molecular mechanisms responsible.