Section of Nephrology, Department of Internal Medicine, Amsterdam UMC location, University of Amsterdam, Amsterdam, The Netherlands.
Microcirculation, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Am J Physiol Renal Physiol. 2023 Dec 1;325(6):F707-F716. doi: 10.1152/ajprenal.00076.2023. Epub 2023 Oct 5.
Blood pressure (BP) responses to sodium intake show great variation, discriminating salt-sensitive (SS) from salt-resistant (SR) individuals. The pathophysiology behind salt sensitivity is still not fully elucidated. We aimed to investigate salt-induced effects on body fluid, vascular tone, and autonomic cardiac response with regard to BP change in healthy normotensive individuals. We performed a randomized crossover study in 51 normotensive individuals with normal body mass index and estimated glomerular filtration rate. Subjects followed both a low-Na diet (LSD, <50 mmol/day) and a high-Na diet (HSD, >200 mmol/day). Cardiac output, systemic vascular resistance (SVR), and cardiac autonomous activity, through heart rate variability and cross-correlation baroreflex sensitivity (xBRS), were assessed with noninvasive continuous finger BP measurements. In a subset, extracellular volume (ECV) was assessed by iohexol measurements. Subjects were characterized as SS if mean arterial pressure (MAP) increased ≥3 mmHg after HSD. After HSD, SS subjects (25%) showed a 6.1-mmHg (SD 1.9) increase in MAP. No differences between SS and SR in body weight, cardiac output, or ECV were found. SVR was positively correlated with Delta BP ( = 0.31, = 0.03). xBRS and heart rate variability were significantly higher in SS participants compared to SR participants after both HSD and LSD. Sodium loading did not alter heart rate variability within groups. Salt sensitivity in normotensive individuals is associated with an inability to decrease SVR upon high salt intake that is accompanied by alterations in autonomous cardiac regulation, as reflected by decreased xBRS and heart rate variability. No discriminatory changes upon high salt were observed among salt-sensitive individuals in body weight and ECV. Extracellular fluid expansion in normotensive individuals after salt loading is present in both salt-sensitive and salt-resistant individuals and is not discriminatory to the blood pressure response to sodium loading in a steady-state measurement. In normotensive subjects, the ability to sufficiently vasodilate seems to play a pivotal role in salt sensitivity. In a normotensive cohort, differences in sympathovagal balance are also present in low-salt conditions rather than being affected by salt loading. Whereas treatment and prevention of salt-sensitive blood pressure increase are mostly focused on renal sodium handling and extracellular volume regulation, our study suggests that an inability to adequately vasodilate and altered autonomous cardiac functioning are additional key players in the pathophysiology of salt-sensitive blood pressure increase.
血压（BP）对钠摄入量的反应差异很大，可将盐敏感（SS）与盐抵抗（SR）个体区分开来。盐敏感性背后的病理生理学仍未完全阐明。我们旨在研究健康的正常血压个体中钠诱导对体液、血管张力和自主心脏反应的影响，以了解血压变化。我们在 51 名正常体重指数和估计肾小球滤过率的正常血压个体中进行了一项随机交叉研究。受试者分别遵循低钠饮食（LSD，<50mmol/天）和高钠饮食（HSD，>200mmol/天）。通过非侵入性连续手指血压测量评估心输出量、全身血管阻力（SVR）和心脏自主活动，包括心率变异性和交叉相关压力反射敏感性（xBRS）。在一个亚组中，通过碘海醇测量评估细胞外体积（ECV）。如果平均动脉压（MAP）在 HSD 后增加≥3mmHg，则将个体确定为 SS。在 HSD 后，25%的 SS 受试者（MAP 增加 6.1mmHg[标准差 1.9]）。SS 和 SR 受试者之间在体重、心输出量或 ECV 方面没有差异。SVR 与ΔBP 呈正相关（r=0.31，P=0.03）。与 SR 受试者相比，SS 受试者在 HSD 和 LSD 后，xBRS 和心率变异性均显著升高。高盐摄入并未改变组内的心率变异性。正常血压个体中的盐敏感性与不能在高盐摄入时降低 SVR 相关，这伴随着自主心脏调节的改变，反映为 xBRS 和心率变异性降低。在盐敏感个体中，在高盐状态下没有观察到体重和 ECV 之间的有区别的变化。正常血压个体在盐负荷后细胞外液扩张存在于盐敏感和盐抵抗个体中，并且在稳态测量中不能区分对钠负荷的血压反应。在正常血压受试者中，充分血管舒张的能力似乎在盐敏感性中起着关键作用。在正常血压队列中，低盐条件下也存在交感神经-迷走神经平衡的差异，而不是受盐负荷的影响。虽然盐敏感血压升高的治疗和预防主要集中在肾脏钠处理和细胞外液调节上，但我们的研究表明，不能充分血管舒张和自主心脏功能改变是盐敏感血压升高病理生理学的另外两个关键因素。
