Abstract P3027: Response to Exercise Dictates Metabolic and Microbiotal Effects of a High-Salt Diet With Aging

Individual variation in response to exercise could be critical to sustaining cardiorespiratory fitness with aging. In order to explore this idea, we developed preclinical animal models of low and high response trainer rats (LRT and HRT, respectively) by selective breeding based on change (Δ) in performance on a maximal treadmill running test after an 8-week standardized aerobic training program. To test the hypothesis that individuals with low adaptive capacity to exercise training (like LRT rats) are more vulnerable to the development of hypertension associated with aging compared to individuals with high adaptive ability (like HRT rats), we subjected 24-month old male rats to a high-salt diet (HSD, 2% NaCl) for 32 days and evaluated cardiovascular and metabolic responses. We observed no significant change in resting blood pressure (telemetry implants, DSI) after HSD suggesting neither strain is salt-sensitive (LRT vs. HRT before HSD, 115.9 vs. 120.8; after HSD, 112.4 vs. 118.4 mmHg). However, resting heart rate decreased in both strains in response to HSD (ΔLRT = -32.2 bpm and ΔHRT = -30.9 bpm). Metabolic evaluation (CLAMS, Columbus Instruments) showed LRT rats significantly decreased food intake (ΔLRT vs. ΔHRT, -9.64 vs. 3.86 g/kg/day; P < 0.01) and water consumption (ΔLRT vs. ΔHRT, -11.8 vs. 7.5 ml/kg/day; P < 0.05) after HSD compared to HRT. Interestingly, we found that the respiratory exchange ratio (RER) was significantly lowered in LRT rats (before HSD, 0.95; after HSD, 0.90; P < 0.05), but a trend of increasing RER occurred in HRT rats after HSD. Accordingly, we observed opposite and inverse trends in fat and glucose oxidation indicating that aged LRT and HRT rats reprioritize energy metabolism differently in response to HSD. Both strains maintained their normal body weight and plasma concentration of sodium while coping with HSD. In addition, 16S rRNA profiling of fecal samples revealed that the relative abundance of several gut bacteria including Lactobacillaceae and Turicibacteraceae increased in LRT rats (ΔLRT, 5.6% and 4.6% respectively) but not in HRT rats. Together, these data suggest that rats bred for their ability to respond to exercise adapt differently to a HSD in order to maintain cardiovascular and metabolic homeostasis.