Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Experimental and Clinical Research Center, Max-Delbrück Center for Molecular Medicine, Charité Medical Faculty, Berlin, Germany.
Kidney Int. 2017 Jun;91(6):1324-1335. doi: 10.1016/j.kint.2017.02.034.
Blood pressure salt sensitivity and salt resistance are mechanistically imperfectly explained. A prescient systems medicine approach by Guyton and colleagues-more than 50 years ago-suggested how salt intake might influence blood pressure. They proposed that a high-salt diet engenders sodium accumulation, volume expansion, cardiac output adjustments, and then autoregulation for flow maintenance. The autoregulation in all vascular beds increases systemic vascular resistance, causing the kidneys to excrete more salt and water, thus reducing systems to normal and minimizing any changes in blood pressure. This schema, which is remarkably all encompassing, included all regulatory mechanisms Guyton could identify at the time. Guyton introduced the idea that the kidney is central, particularly concerning the regulation of renal pressure natriuresis. Numerous criticisms have been subsequently raised, particularly recently. Kurtz and colleagues argue that the ability of individuals to respond with an appropriate vasodilatory response to increased salt intake is pivotal. Data exist to address that issue. Salt-resistant hypertensive models provide additional information. We identified a mendelian form of hypertension not related to sodium reabsorption in the distal nephron. The hypertension develops because of increased systemic vascular resistance. In addition, we rediscovered a third salt-storage glycose-aminoglycan-related compartment, largely in the skin. This compartment operates independently of renal function, and when perturbed, is associated with salt sensitivity. More recently, we found novel molecular mechanisms demonstrating how large salt quantities are excreted by the kidneys with minimal water losses. We introduce novel interpretations as to how the kidneys excrete salt when the intake is high. The findings could have relevance as to how blood pressure may be regulated at varying salt intakes. Our purposes are to provide the readership with a banquet of thoughts to digest, to pursue Guyton's ideas, and to adjust them accordingly.
血压盐敏感性和盐抵抗的机制解释并不完善。50 多年前，盖顿（Guyton）及其同事前瞻性地采用系统医学方法，提出了盐摄入量如何影响血压的观点。他们提出，高盐饮食会导致钠积累、容量扩张、心输出量调整，然后通过自身调节来维持流量。所有血管床的自身调节都会增加全身血管阻力，导致肾脏排泄更多的盐和水，从而使系统恢复正常，并最大限度地减少血压变化。这个方案非常全面，包括了盖顿当时能识别的所有调节机制。盖顿提出了肾脏是核心的观点，特别是在肾脏压力排钠的调节方面。此后，人们提出了许多批评意见，尤其是最近。库尔茨（Kurtz）及其同事认为，个体对增加盐摄入做出适当的血管扩张反应的能力至关重要。现有数据可以解决这个问题。盐抵抗性高血压模型提供了更多信息。我们发现了一种与远端肾单位钠重吸收无关的孟德尔形式的高血压。这种高血压的发展是由于全身血管阻力增加。此外，我们重新发现了第三个与糖胺聚糖相关的盐储存部位，主要位于皮肤中。这个部位独立于肾功能运作，当受到干扰时，与盐敏感性有关。最近，我们发现了新的分子机制，表明肾脏如何在最小的水损失下排泄大量盐。我们提出了新的解释，说明肾脏在摄入高盐时如何排泄盐。这些发现可能与血压在不同盐摄入量下的调节方式有关。我们的目的是为读者提供一个思想盛宴，以消化盖顿的观点，并相应地调整它们。
