Exercise, but not statins improve vasodilation in obesity‐induced endothelial dysfunction in Wistar rats

Statins are important medications for the prevention of cardiovascular disease (CVD). Exercise is a hallmark of a healthy lifestyle and reduces CVD burden. Interestingly, statins impaired exercise induced skeletal muscle adaptations. The peripheral effects of exercise training are not limited to skeletal muscle but also improve endothelium‐dependent vasodilation in conduit arteries. Whether the previously observed interaction between statins and exercise alters the vascular adaptations to exercise training is currently unclear. We assessed whether statins influence the beneficial effects of exercise training on vascular function in obesity induced endothelial dysfunction in male Wistar rats. Methods A total of 46 male eight week‐old Wistar rats received a high‐fat diet (60% fat/1% cholesterol) for a total of 20 weeks. After eight weeks animals were randomized into four groups: sedentary control (SED; n =11) and exercise (EX; n =11), sedentary with statin (SED/STAT; n =13) and exercise with statin (EX/STAT; n= 11). Simvastatin (10 mg/kg/day for 12 weeks) was added to the drinking water. Animals exercised for 12 weeks, 5 days/week for 1 hour/day at a speed of 18 m/min in a motorized running wheel. All animals were weighed weekly. Drinking water consumption was assessed in a subgroup of animals. Plasma cholesterol content was measured by standard enzymatic method. Endothelium‐dependent (acetylcholine [Ach]) and – independent (sodium‐nitroprusside [SNP]) vascular function was assessed in the abdominal aorta using in vitro myography. Results Drinking water consumption was not different between groups. Statin treated animals had lower cholesterol levels (SED: 2.6 95%‐confidence interval (CI): 2.3 to 2.8 mmol/L vs. SED/STAT: 2.2 95%‐CI: 2.0 to 2.4 mmol/L, p = 0.04, and EX/STAT: 2.1 95%‐CI: 1.9 to 2.4 mmol/L, p = 0.01). Statin treatment did not influence exercise duration and intensity. Statins augmented the exercise induced reduction in weight gain (SED: 354 95%‐CI: 322 to 387 g vs. EX: 302 95%‐CI: 268 to 336 g [p = 0.03] and EX/STAT: 237 (204 95%‐CI: 204 to 272 g [p < 0.001]). Exercise training independent of statin treatment increased maximal Ach‐induced vasodilation (SED: 57.5 95%‐CI: 51.2 to 63.8%; EX: 77.0 95%‐CI: 69.5 to 84.6% [p < .01], EX/STAT: 75.1 95%‐CI: 68.8 to 81.4 % [p < .01]). Simvastatin treatment alone did not improve Ach‐induced vasodilation compared to control (63.5 95%‐CI: 57.5 to 69.8 [p = .17]). Statins and exercise reduced Ach‐induced EC50 compared to SED but not EX/STAT (SED: 1.91E‐5 95%‐CI: 2.42E‐5 to 1.21E‐5 log[M] vs. EX: 7.75E‐6 95%‐CI: 1.50E‐5 to 5.31E‐7 log[M] vs. STAT: 5.32E‐6 95%‐CI: 1.11E‐5 to 4.35E‐7 log[M]). SNP‐induced vasodilation was not influenced by exercise or statins (SED: 83.8 95%‐CI: 79.2 to 88.5 % vs EX: 84.8 95%‐CI: 79.2 to 90.4 % vs. STAT: 81.2 95%CI: 76.7 to 85.6 % vs. STAT/EX: 85.5 95%‐CI: 80.9 to 90.2 %). Conclusion Statin treated animals had lower cholesterol levels. Statins and exercise had a synergistic effect on high‐fat induced weight gain. The lowest weight gain was observed in animals treated with statins and exercise. However, statin and exercise alone also reduced weight gain. Exercise training improved endothelium‐dependent vasodilation independent of statin treatment. Statins alone were unable to overcome the obesity‐induced endothelial‐dysfunction. Therefore, exercise is essential to maintain endothelial function in rats with high cardiometabolic risk independent of statin treatment. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .