Sodium Pump Inhibitors In Blood Pressure Regulation

我们研究了在收缩压中度升高（SBP：139+/-2; DBP：83+/-2 mmHg）的中老年人（8名男性和3名女性; 60+/-2岁）中进行的饮食NaCl限制的影响。我们测量了尿和血浆MBG水平、SBP、aPWV（随机、安慰剂对照、交叉设计）。我们还探索了5周低氯化钠（LS; 77+/-9 mmol/天）和5周正常氯化钠（NS; 144+/-7 mmol/天）饮食条件下MBG排泄与SBP和aPWV的相关性。还评估了氧化应激的标志物。 5周低钠饮食与5周正常钠饮食相比，SBP（127+/-3 mmHg vs. 138+/- 5 mmHg; P<0.05）和aPWV（700+/-40 cm/sec vs. 843 +/- 36 cm/sec，降低17%，P<0.05）降低（随机，交叉设计）。LS组尿MBG排泄量（每周测量）低于NS组（25.4+/-1.8 pmol/kg/d vs. 30.7+/-2.1 pmol/kg/d，p<0.05），并且在10周内与SBP（r=0.39，p<0.001）和钠排泄量（r = 0.46，p<0.001）呈正相关。 这些关系在NS条件下持续存在，但在LS条件下不存在（p<0.005）。 MBG排泄量与aPWV（r=0.51，p<0.05）和内皮细胞氧化酶NAD（P）H氧化酶-p47 phox表达（r=0.53，p<0.05）呈正相关。 总之，目前的结果表明，饮食钠限制减少肾脏MBG排泄中老年人中度升高的收缩压。我们的研究结果表明，这种MBG的减少可能有助于，可能通过减少氧化应激，以减少大弹性动脉硬度和收缩压，伴随饮食钠减少。 鉴于年龄相关的动脉僵硬度，SBP和盐敏感性增加，这些结果呼应了最近呼吁减少美国饮食中的钠摄入量，特别是在快速增长的中老年人高危人群中。 这些结果首次表明，在人类中，饮食盐限制减少了MBG排泄，这与SBP和aPWV的降低以及血管弹性的改善有关。 此外，在典型的美国饮食钠摄入期间，MBG与SBP呈正相关，这补充了啮齿动物/人类喂食实验性高钠饮食的现有证据。

We studied the effect of dietary NaCl restriction performed in middle-aged/older adults (8 men and 3 women; 60+/-2 yrs) with moderately elevated systolic BP (SBP: 139+/-2; DBP: 83+/-2 mmHg). We measured urinary and plasma MBG levels, SBP, aPWV (randomized, placebo-controlled, cross-over design). We also explored the associations of MBG excretion with SBP and aPWV across conditions of 5 weeks of a low NaCl (LS; 77+/-9 mmol/day) and 5 weeks of a normal NaCl (NS; 144+/-7 mmol/day) diet. Markers of oxidative stress were also assessed. SBP (127+/-3 mmHg vs. 138+/- 5 mmHg; P<0.05) and aPWV (700+/-40 cm/sec vs. 843 +/- 36 cm/sec, 17% of reduction, P<0.05) were reduced following a 5-week low sodium vs. 5-week normal sodium diet (randomized, cross-over design). Urinary MBG excretion (weekly measurements) was lower during the LS vs. NS condition (25.4+/-1.8 vs. 30.7+/-2.1 pmol/kg/day, p<0.05) and was positively correlated with SBP (r=0.39, p<0.001) and sodium excretion (r = 0.46, p<0.001) across the 10 weeks. These relations persisted during the NS but not the LS condition (p<0.005). MBG excretion also was positively related to aPWV (r=0.51, p<0.05) and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase-p47phox (r=0.53, p<0.05). In summary, the present results demonstrate that dietary sodium restriction reduces renal MBG excretion in middle-aged and older adults with moderately elevated systolic blood pressure. Our findings suggest that this reduction in MBG may contribute, possibly via reduced oxidative stress, to the reductions in large elastic artery stiffness and SBP that accompanied dietary sodium reduction. Given age-associated increases in arterial stiffness, SBP and salt sensitivity, these results echo recent calls for reduced sodium intake in the American diet, particularly in the rapidly growing, at-risk population of middle-aged and older adults. These results show, for the first time in humans, that dietary salt restriction reduces MBG excretion, and this is associated with reductions in SBP and aPWV, and with improved elasticity of blood vessels. In addition, MBG is positively related to SBP during sodium intake typical of an American diet, complimenting existing evidence in rodents/humans fed experimentally high sodium diets.