Voluntary Exercise Attenuates Reactive Oxygen Species Mediated Endothelial Dysfunction in Rodents Fed a High Sodium Diet Independent of Blood Pressure
Voluntary Exercise Attenuates Reactive Oxygen Species Mediated Endothelial Dysfunction in Rodents Fed a High Sodium Diet Independent of Blood Pressure
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自愿运动可减轻高钠饮食啮齿类动物活性氧介导的内皮功能障碍，与血压无关
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发表时间：
2016
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通讯作者：
S. Lennon
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作者：
J. Guers;Lauren Kasecky‐Lardner;W. Farquhar;D. Edwards;S. Lennon
高钠饮食已被证明会导致内皮功能障碍，并降低一氧化氮的生物利用度，而不依赖于血压(BP)。这种有害的影响与活性氧物种(ROS)的增加有关。众所周知，运动对血管内皮细胞功能有好处。这可能部分归因于ROS产量的减少。这项研究的目的是验证这样一种假设，即自愿车轮运行通过降低ROS而防止高钠对内皮功能的有害影响，而不依赖于BP。8周龄雄性SD大鼠分为正常钠组(NS，0.4%)和高钠组(HS，4.0%)，每组6周。节食组被进一步细分为久坐组(NS，HS)或运动组(NS-EX，HS-EX)，后者被放在一个24小时可接触转轮的笼子里。每周测量3次血压，两组均无变化。分别在基线和6周时采集血和尿，以评估血钠和尿钠。6周后处死动物，以乙酰胆碱(ACh)、超氧化物歧化酶清除剂Temol和NADPH氧化酶抑制剂载脂蛋白(Apo)存在或不存在时的血管内皮依赖性松弛(EDR)为评价指标。测定比目鱼肌中柠檬酸合成酶(CS)的活性。与NS组相比，HS组血钠和尿钠浓度升高(p<；0.05)。两个运动组的CS活性都较高，表明有训练效果(p<；0.05)。HS(n=11)大鼠股骨EDR较NS(n=10)大鼠降低，表现为最大反应减弱(Emax：HS 39.4%±4.8 vs NS 66.9%±3.9；p<；0.05)。与单纯使用HS相比，temol(HS+T，65.9%±5.6；p<；0.05)和Apo(HS+Apo，62.9%±10.9；p<；0.05)改善了eMax。以曲线下面积(AUC)表示的总EDR在加入temol后增加，但差异无统计学意义(AUC：HS，63.8%±8.1 vs HS+T，89.6%±8.02；p=0.06)。运动使Emax在HS饮食(HS-EX(n=8)，76.8%±7.3vs HS，39.4%±4.8；p<；0.05)和AUC(AUC：HS-EX，127.1%±0.1vs HS，63.8%±8.1；p<；0.05)存在的情况下拯救。在运动组中，添加坦普尔和/或载脂蛋白总体上对EDR有负面影响。在HS-EX组，加入temol后AUC降低(p<；0.05)，而在NS-ex组(n=10)，给予Apo则降低AUC(p<；0.05)。丹参酚和载脂蛋白均显著降低NS-EX动物的Emax。综上所述，HS通过NADPH氧化酶介导的ROS损伤EDR。自愿的车轮运行可能通过减少ROS来恢复EDR。运动组的EDR随着抗氧化剂的加入而减少，这表明可能存在维持正常血管功能所需的临界水平的ROS。
High sodium diets have been shown to cause endothelial dysfunction and diminish nitric oxide bioavailability independent of blood pressure (BP). This deleterious effect has been linked to increases in reactive oxygen species (ROS). Exercise is known for its beneficial effect on endothelial function. This may be due, in part, to a reduction in ROS production. The purpose of this study was to test the hypothesis that voluntary wheel running prevents the deleterious effect of high sodium on endothelial function by reducing ROS independent of BP. Eight week old male Sprague‐Dawley rats were placed on either a normal sodium (NS, 0.4%) or high sodium (HS, 4.0%) diet for 6 weeks. Diet groups were further subdivided into a sedentary (NS, HS) or exercise group (NS‐EX, HS‐EX), the latter were placed in a cage with 24‐hour access to a running wheel. BP was measured 3 times per week and did not change in any group. Blood and urine were collected at baseline and 6 weeks in order to assess serum and urinary sodium. Animals were sacrificed after 6 weeks and endothelium‐dependent relaxation (EDR) was assessed by dose response to acetylcholine (ACh), in the presence and absence of the superoxide scavenger tempol and the NADPH oxidase inhibitor apocynin (Apo) in femoral rings. Citrate synthase (CS) activity was measured in the soleus muscle. Serum and urinary sodium concentrations were elevated in HS groups relative to NS (p<0.05). CS activity was greater in both exercise groups indicating a training effect (p < 0.05). Femoral EDR was reduced in HS (n=11) compared to NS (n=10) rats as demonstrated by an attenuated maximal response (Emax: HS, 39.4% ± 4.8 vs. NS, 66.9% ± 3.9; p < 0.05). Emax was improved by tempol (HS+T, 65.9% ± 5.6; p <0.05) and Apo (HS+Apo, 62.9% ± 10.9; p <0.05) compared to HS alone. Total EDR as assessed by area under the curve (AUC) increased in HS animals with the addition of tempol but did not quite reach significance (AUC: HS, 63.8% ± 8.1 vs. HS+T, 89.6% ± 8.02; p=0.06). Exercise rescued Emax in the presence of a HS diet (HS‐EX (n=8), 76.8% ± 7.3 vs. HS, 39.4% ± 4.8; p<0.05) and AUC (AUC: HS‐EX, 127.1% ± 0.1 vs. HS, 63.8% ± 8.1; p <0.05). The addition of tempol and/or Apo had negative effects in general on EDR in the exercise groups. AUC was diminished in the HS‐EX group with the addition of tempol (p<0.05), while the administration of Apo decreased AUC in NS‐EX (n=10) (p < 0.05). Both tempol and apocynin decreased Emax significantly in NS‐EX animals. In conclusion, HS impairs EDR through NADPH oxidase meditated ROS. Voluntary wheel running restored EDR likely through a reduction in ROS. EDR was diminished in the exercising groups with the addition of antioxidants suggesting there may be a critical level of ROS needed for maintenance of normal vascular functioning.