Sirtuins are regulators of eNOS and endothelial function; however, no studies have examined the influence of exercise on sirtuin regulation of endothelial function. Effects of the novel sirtuin inhibitor, salermide, on vascular reactivity in rat aortas were investigated following exercise training of different durations. Male Wistar rats (8–9 months old) were divided into four groups (n = 10–12/group): sedentary (SED), 1 day (1D), 2 weeks (2WK), or 6 weeks (6WK) of exercise. Exercise consisted of running on a motor-driven treadmill at 15 m/min, 15% grade, for 40 min (1D) increased up to 1 h at the end of 2 weeks (2WK) and sustained for an additional 4 weeks (6WK). Dose responses to phenylephrine, sodium nitroprusside, and acetylcholine in the presence or absence of salermide (30 µM) were analyzed. SIRT1 and eNOS protein expression as well as nitrotyrosine levels were determined by immunoblotting. Superoxide dismutase activity was determined by colorimetric assay. Sirtuin inhibition significantly impaired acetylcholine-induced vasorelaxtion in aortas in SED, 1D, and 2WK endurance trained rats but not in 6WK. eNOS expression significantly increased ~ 2.0-fold in 1D, 2WK, and 6WK groups. SIRT1 expression and 3-nitrotyrosine levels were significantly increased in 1D and 2WK but were not significantly elevated in 6WK. SOD levels were significantly elevated in 6WK. These data suggest that chronic endurance training diminishes the role of sirtuins in regulating endothelium-dependent relaxation and appears to be related to changes in SIRT1 expression as well as redox status.

Sirtuins 是 eNOS 和内皮功能的调节剂；然而，尚无研究探讨运动对沉默调节蛋白调节内皮功能的影响。在不同持续时间的运动训练后，研究了新型去乙酰化酶抑制剂萨勒胺对大鼠主动脉血管反应性的影响。雄性 Wistar 大鼠（8-9 个月大）分为四组（ n = 10-12/组）：久坐 (SED)、1 天 (1D)、2 周 (2WK) 或 6 周 (6WK) 运动。锻炼包括在电动跑步机上以 15 m/min、15% 坡度跑步 40 分钟 (1D)，在 2 周结束时增加至 1 小时 (2WK)，并持续另外 4 周 (6WK) 。分析了在存在或不存在萨勒胺 (30 µM) 的情况下对去氧肾上腺素、硝普钠和乙酰胆碱的剂量反应。通过免疫印迹法测定 SIRT1 和 eNOS 蛋白表达以及硝基酪氨酸水平。通过比色测定法测定超氧化物歧化酶活性。在 SED、1D 和 2WK 耐力训练的大鼠中，Sirtuin 抑制显着损害乙酰胆碱诱导的主动脉血管舒张，但在 6WK 训练的大鼠中则不然。在 1D、2WK 和 6WK 组中，eNOS 表达显着增加约 2.0 倍。 SIRT1 表达和 3-硝基酪氨酸水平在 1D 和 2WK 中显着增加，但在 6WK 中没有显着升高。 SOD 水平在 6WK 内显着升高。这些数据表明，长期耐力训练会减弱去乙酰化酶在调节内皮依赖性松弛中的作用，并且似乎与 SIRT1 表达和氧化还原状态的变化有关。