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R6102 --> 602.13 --> Exercise is used as a therapeutic option to improve an individual's quality of life or as a method to attenuate the severity of cardiovascular, respiratory, or metabolic‐related diseases. However, changes in cardiorespiratory fitness in response to endurance training are often heterogenous with individuals being more or less responsive to a similar exercise protocol. Heterogeneity in responses to exercise training is observed in humans and rodents. Low responses to training might be mitigated by modifying the standard exercise training protocol by altering the frequency, intensity, or duration of training. Threshold‐based exercise training prescription, e.g., critical speed, has also been proposed as a means to reduce the variability of training responses. The aim of this study was to identify the effect of different exercise training intensities on changes in exercise capacity in two inbred strains of mice, NZW/LacJ (NZW) and FVB/NJ (FVB). NZW mice were selected because they respond poorly to moderate intensity endurance exercise whereas, FVB mice respond well to endurance training. We hypothesized that increasing the intensity of the training would reduce the number of low or non‐responding NZW mice. To test this hypothesis, female mice from each strain were assigned to one of three treadmill training groups based on critical speed (CS): 80% of their critical speed (CS80%), 90% of their critical speed (CS90%), or sedentary controls (SED). Exercise groups within each strain were volume matched and thus ran the same distance over the 6‐week training period. Pre‐training exercise capacity differed between NZW (30.5 ± 3.5 min) and FVB (36.1 ± 2.8 min) mice (P < 0.001). Critical speeds also differed between strains (NZW: 25.1 ± 2.4 m/min; FVB: 32.9 ± 1.6 m/min, P < 0.001). After training, both FVB exercise groups, CS80% (10.0 ± 4.9 min, P = 0.004) and CS90% (14.0 ± 7.7 min, P = 0.007), improved their endurance capacity. In contrast, NZW CS80% did not significantly improve after training (0.4 ± 4.6 min), but NZW CS90% improved significantly (3.6 ± 2.7 min, P = 0.02). Collectively, these data indicate that the high‐responder FVB strain can adapt to moderate‐intensity and high‐intensity endurance training. The low‐responder NZW strain only showed significant improvement after sufficient homeostatic stress was induced through high‐intensity endurance training. These data suggest that increasing exercise intensity can improve responses to exercise training in low‐ or non‐responding mice. [ABSTRACT FROM AUTHOR]

R5806 --> 602.11 --> An impaired endothelial function is a fundamental component of the pathogenesis of cardiovascular disease. In mice, exercise training is well‐known to improve cardiorespiratory fitness and endothelial function. However, the post exercise training effect on endothelial function varies among different strains of mice, suggesting that genetic background contributes to the heterogeneous effect of exercise on vascular health. NZW/LacJ (NZW) mice are known as relatively low responders to exercise training compared to high responder strains such as FVB/NJ (FVB). NZW mice also have relatively poor endothelial function in thoracic aorta when compared with other mouse strains. Therefore, we aimed to determine the contribution of genetic background to endothelial adaptation to exercise training in FVB and NZW mice. Vasoreactivity was assessed in femoral arteries from female mice from both strains (NZW and FVB) after 6 weeks of training using two different critical speed (CS) treadmill training intensities. Mice from each strain were randomly assigned to one of three groups: sedentary (SED), 80% of CS training (CS80), and 90% of CS (CS90) training. After training, endothelium‐dependent vasorelaxation to acetylcholine (ACh) and endothelium‐independent vasorelaxation to sodium nitroprusside (SNP) were measured as well as the vasocontractile responses to phenylephrine (PE) and potassium chloride (KCl). Maximal relaxation responses and IC50 for ACh and SNP were similar between NZW groups (SED, CS80, and CS90). In femoral arteries from FVB mice, there were no differences for maximal relaxation to ACh, but there was significant difference in IC50 for ACh‐induced vasorelaxation between SED vs. CS90 groups (p=0.05). Maximal responses to ACh were similar between NZW and FVB; however, IC50 was significantly lower in FVB compared with NZW, indicating that sensitivity to ACh is greater in arteries from FVB. There was a significant strain‐dependent difference for IC50 for SNP despite no strain differences for maximal responses. There was no effect of exercise or strain on contractile responses to PE and KCl, although the EC50 for KCl induced vasocontraction was higher (p=0.0329) in NZW. Treadmill exercise training at 80% or 90% CS did not contribute to improved vasomotor function in NZW while higher intensity exercise improved sensitivity to ACh in arteries from FVB. Genetic background did not significantly impact vasomotor function or endothelial responses to exercise training in FVB and NZW mice. [ABSTRACT FROM AUTHOR]