血压的纵向变化先于白蛋白尿的变化，而增加饮食中的钠摄入量会加速这一变化。
Longitudinal changes in blood pressure are preceded by changes in albuminuria and accelerated by increasing dietary sodium intake.
机构信息
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Laboratory of Experimental Hypertension, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
出版信息
Exp Gerontol. 2023 Mar;173:112114. doi: 10.1016/j.exger.2023.112114. Epub 2023 Feb 6.
BACKGROUND
Dietary sodium is a well-known risk factor for cardiovascular and renal disease; however, direct evidence of the longitudinal changes that occur with aging, and the influence of dietary sodium on the age-associated alterations are scarce.
METHODS
C57BL/6 mice were maintained for 13 months on a low (LS, 0.02 % Na), normal (NS, 0.3 % Na) or high (HS, 1.6 % Na) salt diet. We assessed 1) the longitudinal trajectories for two markers of cardiovascular and renal dysfunction (blood pressure (BP) and albuminuria), as well as hormonal changes, and 2) end-of-study cardiac and renal parameters.
RESULTS
The effect of aging on BP and kidney damage did not reach significance levels in the LS group; however, relative to baseline, there were significant increases in these parameters for animals maintained on NS and HS diets, starting as early as month 7 and month 5, respectively. Furthermore, changes in albuminuria preceded the changes in BP relative to baseline, irrespective of the diet. Circulating aldosterone and plasma renin activity displayed the expected decreasing trends with age and dietary sodium loading. As compared to LS - higher dietary sodium consumption associated with increasing trends in left ventricular mass and volume indices, consistent with an eccentric dilated phenotype. Functional and molecular markers of kidney dysfunction displayed similar trends with increasing long-term sodium levels: higher renovascular resistance, increased glomerular volumes, as well as higher levels of renal angiotensin II type 1 and mineralocorticoid receptors, and lower renal Klotho levels.
CONCLUSION
Our study provides a timeline for the development of cardiorenal dysfunction with aging, and documents that increasing dietary salt accelerates the age-induced phenotypes. In addition, we propose albuminuria as a prognostic biomarker for the future development of hypertension. Last, we identified functional and molecular markers of renal dysfunction that associate with long-term dietary salt loading.
背景
膳食钠是心血管和肾脏疾病的一个众所周知的危险因素；然而，随着年龄的增长而发生的纵向变化的直接证据，以及膳食钠对与年龄相关的改变的影响却很少。
方法
C57BL/6 小鼠在低（LS，0.02%Na）、正常（NS，0.3%Na）或高（HS，1.6%Na）盐饮食中维持 13 个月。我们评估了 1）两种心血管和肾功能障碍标志物（血压（BP）和蛋白尿）以及激素变化的纵向轨迹，以及 2）研究结束时的心脏和肾脏参数。
结果
在 LS 组中，衰老对 BP 和肾脏损伤的影响没有达到显著水平；然而，与基线相比，维持在 NS 和 HS 饮食的动物的这些参数有显著增加，分别从第 7 个月和第 5 个月开始。此外，与基线相比，无论饮食如何，蛋白尿的变化都先于 BP 的变化。循环醛固酮和血浆肾素活性随年龄和膳食钠负荷的增加呈下降趋势。与 LS 相比 - 较高的膳食钠消耗与左心室质量和体积指数的增加趋势相关，与偏心扩张表型一致。肾功能障碍的功能和分子标志物随着长期钠水平的升高呈现出相似的趋势：更高的肾血管阻力、肾小球体积增加，以及更高水平的肾血管紧张素 II 型 1 和盐皮质激素受体，以及更低的肾 Klotho 水平。
结论
我们的研究提供了与衰老相关的心肾功能障碍发展的时间表，并证明增加膳食盐加速了与年龄相关的表型。此外，我们提出蛋白尿作为未来高血压发展的预后生物标志物。最后，我们确定了与长期膳食盐负荷相关的肾功能障碍的功能和分子标志物。
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