Salt Sensitivity: Common Findings

There are five broad categories consistently associated with salt sensitivity. These include demographic factors, racial and social factors, renal function factors, hormonal factors, and dietary habit factors (Table II).

There is a direct, positive relationship between age and salt sensitivity, with increasing salt sensitivity noted in older subjects. While salt sensitivity is usually perceived as a phenomenon occurring in mid-life or later (i.e., after age 45), it has also been documented in Caucasian adolescents who are overweight.[17,18,19] Weight may also be responsible for the gender differences noted in blood pressure response to sodium. Women are usually found to be more salt-sensitive than men. However, as Weinberger[9] noted, all studies examining salt sensitivity administered the same amount of sodium to both men and women. Women typically weigh less than men and, therefore, may have been subjected to a greater salt load based on body weight, making it more likely that a blood pressure response would be noted in women. However, most studies have shown that regardless of sodium intake and the presence or absence of hypertension, salt-sensitive subjects tend to weigh more than salt-resistant subjects.[20] In addition, weight reduction in white adolescents eliminated the sensitivity of blood pressure to sodium.[17]

Salt sensitivity has been found to be more prevalent in young, old, normotensive, and hypertensive African Americans than Caucasians.[13,14,21,22] The increased prevalence of salt sensitivity in African Americans has been demonstrated in studies using i.v. NaCl loading as well as in studies using dietary sodium designs.[10,12,14] The finding of salt sensitivity is so prevalent that it is considered to be a "hallmark" of black hypertension, as salt sensitivity is found in 73% of all African American hypertensive patients.[23]

A number of theories have been postulated, and numerous studies conducted, to determine a biologic or genetic explanation for the significant disparity noted in the prevalence of hypertension among the races. However, research indicates that one genetic hypothesis is insufficient to explain the relationship of salt sensitivity and blood pressure in African Americans. It is argued that race is a social rather than biologic concept, and that factors other than biologic or genetic ones are responsible for the racial differences noted.[24,25,26]

Cooper et al[6] attempted to disentangle the social, environmental, and genetic aspects of race by studying hypertension and sodium intake only in populations of the African diaspora. This international study of seven populations of West African origins revealed a progressive rise in hypertension prevalence, from 16% in West Africa to 26% in the Caribbean and 33% in U.S. This study revealed strong cross-cultural associations of hypertension risk based on social-environmental factors, with obesity and sodium-potassium intake accounting for 70% of the geographic variation in hypertension prevalence. The report did not, however, discuss psychosocial factors that confound the hypertension risk among these subjects. While this study examined only subjects of the African diaspora, it should be noted that the prevalence of hypertension in West Africa (16%) is lower than the rate of hypertension for Caucasians in the U.S. This again highlights the profound importance of environmental exposure in the development of salt sensitivity. It also underscores the fact that salt sensitivity can occur in all racial groups and should be considered a factor with all hypertensive patients.

People with renal insufficiency are more likely to be salt-sensitive, and salt-sensitive subjects are more likely than salt-resistant subjects to have altered intrarenal hemodynamics and glomerular capillary permeability. These alterations include an attenuated rise in glomerular filtration (hyperfiltration) in response to salt loading, and microalbuminuria, which is indicative of glomerular injury.[9,10,12,14] In addition, salt-sensitive persons, particularly women, have suppressed circulating renin levels.[27,28] The end result of this process is a shift in the pressure-natriuresis curve to the right, indicating that salt-sensitive persons require higher systemic pressure to effect the level of natriuresis required to maintain steady-state sodium homeostasis.[8,9,12]

Although there are conflicting data, a number of studies[9,29] have indicated that the sympathetic nervous system may play a role in mediating salt sensitivity. This is based on the findings that many salt-sensitive subjects have higher levels of norepinephrine and decreased levels of dopamine. Norepinephrine is associated with sodium retention and dopamine promotes increased sodium excretion. Both plasma norepinephrine concentrations and urinary sodium excretion are higher among salt-sensitive than salt-resistant subjects.[9,10,30] African American subjects seem to be especially sensitive to the role of dopamine in salt sensitivity. Dopamine is a vasodilator with a natriuretic effect on the kidney. However, when salt-sensitive African Americans are faced with an increased sodium load, they do not have a corresponding increase of dopamine, resulting in increased sodium retention.[28] A similar deficiency of another renal natriuretic/diuretic peptide hormone, kallikrein, has been documented in salt-sensitive individuals. Moreover, although African Americans have a lower level of urinary kallikrein than Caucasians, salt-sensitive whites also have reduced urinary kallikrein excretion.

Dietary habits are also important in the salt sensitivity-blood pressure relationship. Salt-sensitive subjects not only respond differently to increased ingestion of sodium, but also their level of response may be affected by other dietary elements. Salt-sensitive subjects excrete more calcium than salt-resistant subjects while on high salt diets. Researchers have also found that calcium supplementation during normal dietary sodium intake is associated with significantly reduced blood pressure in salt-sensitive and in African American subjects.[10,31] A low level of potassium intake was also associated with increased salt intake, sodium retention, and increased blood pressure. African American men appear to be especially at risk, as diets only marginally deficient in potassium have been associated with salt sensitivity in normotensive black men.[32] Other studies[10,33] have shown that subjects who received a high potassium intake appear to achieve a state of relative salt resistance. It is important to note that high sodium foods are typically low in potassium.