Aging and interaction of natriuretic factors on renal and vascular sodium pump

在第一项临床研究中，39名健康受试者（53 +/- 11岁，男性20人，女性19人）按随机顺序，每天摄入50 mmol（低盐）和150 mmol（高盐）的NaCl，持续4周。在基线（非标准化盐摄入量）和高盐和低盐摄入后测量血浆动脉血压和MBG水平。基线时，血浆MBG （P-MBG）与24小时收缩压（r= 0.43， P=0.007）和舒张压（r=0.32， P=0.047）相关。有趣的是，针对性别的分析显示，这些关系仅在男性中显著。与低盐饮食相比，高盐饮食增加了P- mbg (P=0.029)，主要由男性的结果驱动。男性P- mbg应答者在低盐和高盐摄入之间表现出最大的δ P- mbg，与无应答者相比，收缩压（10.4 +/- 6.4 vs. 0.0 +/- 6.0 mmHg， P=0.003）和舒张压（6.7 +/- 5.0 vs. -0.6 +/- 3.6 mmHg， P=0.001）血压盐敏感性明显增强（低于高盐诱导的P- mbg升高的中位数）。此外，高盐组与低盐组的MBG排泄比例与年龄呈正相关，但与女性无关。我们的结论是，男性MBG随着24小时动脉血压升高而增加，并且4周高盐诱导的MBG反应伴随着盐敏感性的显著增加。然而，这些模式似乎是性别特有的，在人类女性中没有观察到，这与我们之前的出版物（Anderson等）一致。Am J Physiol. 2008)。

In the first clinical study 39 healthy subjects (53 +/- 11 years old; 20 males and 19 females) had a total daily NaCl intake of 50 mmol (low-salt) and 150 mmol (high-salt) for 4 weeks each, in random order. Arterial BP and MBG levels in plasma were measured at baseline (unstandardized salt intake) and after high- and low-salt intake. At baseline, plasma MBG (P-MBG) was related to 24-hour systolic (r= 0.43, P=0.007) and diastolic (r=0.32, P=0.047) BP. Interestingly, gender specific analyses revealed that these relationships were significant in males only. Compared to low-salt, high-salt diet increased P-MBG (P=0.029), mainly driven by results in men. Male P-MBG responders, who demonstrated the largest delta P-MBG between low-salt and high-salt intake, had markedly enhanced systolic (10.4 +/- 6.4 vs. 0.0 +/- 6.0 mmHg; P=0.003) and diastolic (6.7 +/- 5.0 vs. -0.6 +/- 3.6 mm Hg; P=0.001) BP salt-sensitivity vs. non-responders (below median of high-salt induced P-MBG increase), correspondently. In addition, ratio of MBG excretion on a high salt to the low salt positively correlated with age in male participants, but not in female. We concluded that in males MBG increases with 24-hour arterial BP, and 4-week of high-salt induced MBG response is accompanied by marked increase in salt sensitivity. However, these patterns seem to be gender specific and are not observed in females in humans, which is in accordance with our previous publication (Anderson et.al. Am J Physiol. 2008). Next, we salt loaded (2% NaCl in drinking water) 5-month old Wistar rats for 4 weeks (n=16). Rats from the group on a high salt intake were administered vehicle (SALT; n=8) or anti-MBG monoclonal antibody (mAb; 50 ug/kg) (SALT-AB; n=8) during the last week of high salt diet. Eight rats were kept on a normal salt intake for the duration of the study (CTRL group). BP, activity of erythrocyte Na/K-ATPase, levels of MBG in plasma and 24-hr urine, and sensitivity of aortic explants to the vasorelaxant effect of sodium nitropusside (SNP) were measured. Aortic collagen abundance was determined immunohistochemically. In rats from SALT vs. CTRL groups, heightened levels of MBG were associated with inhibition of erythrocyte Na/K-ATPase in the absence of BP changes. High salt intake was accompanied by a 2.5-fold increase in aortic collagen abundance and by a reduction of sensitivity of aortic explants to the vasorelaxant effect of SNP following endothelin-1-induced constriction. In the SALT-AB group, all NaCl-mediated effects were reversed by immunoneutralization of MBG. Thus, high salt intake in young normotensive rats can induce vascular fibrosis via pressure-independent/MBG-dependent mechanisms, and this remodeling is reduced by immunoneutralization of MBG. Thus, age-dependent salt-sensitivity of BP increases in parallel with MBG changes in men, but not in women. In an animal salt-loading study, MBG elevation was associated with fibrosis and reduced relaxation of aorta in the absence of salt-sensitivity in young normotensive rats, indicating that pro-fibrotic effect of MBG may be pressure-independent.