Salt Sensitivity: Causes, Consequences, and Recent Advances

Abstract

Salt (sodium chloride) is an essential nutrient required to maintain physiological functions. However, for most people, daily salt intake far exceeds their physiological need and is habitually greater than recommended upper thresholds. Excess salt intake leads to elevation in blood pressure which drives cardiovascular morbidity and mortality. Indeed, excessive salt intake is estimated to be responsible for ≈5 million deaths per year globally. For approximately one-third of otherwise healthy individuals (and >50% of those with hypertension), the effect of salt intake on blood pressure elevation is exaggerated; such people are categorized as salt sensitive and salt sensitivity of blood pressure is considered an independent risk factor for cardiovascular disease and death. The prevalence of salt sensitivity is higher in women than in men and, in both, increases with age. This narrative review considers the foundational concepts of salt sensitivity and the underlying effector systems that cause salt sensitivity. We also consider recent updates in preclinical and clinical research that are revealing new modifying factors that determine the blood pressure response to high salt intake.

Keywords: glucocorticoids; hypertension; immunity; inflammation; microbiota; potassium; sodium.

Figure 1.

Variability in the blood pressure (BP) response to salt. The percentage change in mean arterial BP was measured in 18 hypertensives following a change from low to high salt intake, with an increase ≥10% as the category threshold. Subjects A and B are salt sensitive with changes of +10.5% and +31% respectively; subject C is salt resistant, with a change of +9.5%. The figure is illustrative of experimental data.

Figure 2.

The long-term impact of a salt-sensitive classification. A, Study showing that salt-sensitive people had more cardiovascular events than nonsalt sensitive. In the salt-sensitive group, there were 17 (5 fatal) cardiovascular events and 14 (3 fatal) in the nonsalt-sensitive group. Reproduced from Morimoto et al with permission. Copyright ©1997, Elsevier. B, Survival curves for normotensive salt-resistant subjects (N+R), normotensive salt-sensitive subjects (N+S), hypertensive salt-resistant subjects (H+R), and hypertensive salt-sensitive subjects (N+S), Normotensive, salt-resistant people had a greater survival than those with hypertension and those with normotension and salt-sensitivity. Reproduced from Weinberger et al with permission. Copyright ©2001, Wolters Kluwer Health, Inc.

Figure 3.

Salt sensitivity, salt balance, and the kidney. A, Negative feedback loop showing control of arterial blood pressure (BP) by renal sodium excretion. B, Servo-control of renal perfusion pressure highlights that the pressure natriuresis mechanism can influence chronic BP regulation. These experiments were performed in conscious dogs. In control animals (blue line), infusion of noradrenaline caused mean arterial pressure to increase by <10 mm Hg and an increase in sodium excretion. In animals with servo-controlled renal perfusion pressure, the BP response to noradrenaline was amplified and sodium excretion did not change. Removal of the servo-control allowed urinary sodium excretion to increase and BP normalized. The figure is illustrative of experimental data. C, The acute pressure natriuresis relationship may be attenuated in salt-sensitive individuals (red line) compared with nonsalt-sensitive people. The supporting evidence comes from studies in salt-sensitive animals, including studies in which major cardiovascular control systems have been experimentally disabled. D, The chronic renal function curve is often rotated and used to infer pressure natriuresis. In fact, the curve shows that salt-sensitive people cannot accommodate large changes in salt intake and BP rises.

Figure 4.

Salt sensitivity and peripheral vascular resistance. Effect of dietary salt loading (250 mmol salt per 70 kg per day) on (A) mean blood pressure (BP), (B) systemic vascular resistance, (C) cardiac output, and (D) cumulative sodium balance, shown as a change from baseline measurements (75 mmol/d salt per 70 kg day). Salt-sensitive individuals do not effectively reduce systemic vascular resistance in response to increasing salt intake. Salt sensitivity was not due to sodium retention and an exaggerated increase in cardiac output. The figure is illustrative of experimental data.