Determinants of Salt Sensitivity in Black and White Normotensive and Hypertensive Women

Abstract

Abstract-Salt sensitivity (SS) has been linked to human hypertension. We examined ethnic differences in the relation between SS; erythrocyte sodium (Na ; and sodium pump activity in African-American (AA) and white women. In a crossover protocol, similar numbers of normotensive, hypertensive, AA, and white women were randomized to 7 days of a 20 meq/d and a Ͼ200 meq/d salt diet (nϭ199). After an overnight inpatient stay, group differences in supine blood pressure (BP), heart rate, erythrocyte cations, and sodium pump activity were measured. The prevalence of SS (53.5% vs 51%) and salt resistance (26.3% vs 30.0%) was similar in both races. Greater mean BP increase with salt loading was seen in AA vs white hypertensives but not between the normotensive women. In hypertensives, increase in mean arterial pressure was 12.6 vs 8.2 mm Hg in AAs vs whites, respectively (PϽ0.01), and for systolic BP, it was 23 vs 14.8 mm Hg (PϽ0.01). Higher Na i were positively correlated with salt responsiveness in AA but not in white women. Sodium pump activity was similar between groups, although the change in maximal activity trended to vary inversely with SS in AA. In closely matched AA and white women, the prevalence of SS is similarly high in both races, although the magnitude of BP increase is greater in AA hypertensives. In AA but not in whites, SS is positively associated with Na ssential hypertension continues to be a major cause of morbidity and mortality in industrialized populations of the world and one for which there is no known cause. In the United States, the prevalence of hypertension increases with age, and at about age 55, the prevalence becomes greater in women versus men. 1 More than half of white and three fourths of African-American (AA) women will develop hypertension by age 65 to 74 years. Acute blood pressure (BP) elevation with increasing salt intake (salt sensitivity [SS]) is commonly reported in large segments of the population, especially in those with renal disease, diabetes, obesity, hypertension, and older age and in AA. 2,3 BP sensitivity to salt might also predict chronic BP elevation, and normotensives with this trait are more likely to develop hypertension. 2,4 However, the pathophysiology of SS and its progression to hypertension remain poorly understood. This is further complicated by the significant heterogeneity in methods of defining SS. [5][6][7][8]20 Increased intracellular sodium ([Na ϩ ] i ,) assessed primarily in circulating blood cells, is one of the most consistently reported abnormalities of cation metabolism in essential hypertension, although a link between intracellular cation metabolism and salt-induced elevation of BP has not been established. A number of epidemiologic studies have documented a direct correlation between [Na ϩ ] i and BP in AA but not in non-AA. 9 -15 Racial differences in several membrane sodium-transport systems have also been reported. 14 -16 Na,KATPase (sodium pump) is a principal regulator of [Na ϩ ] i . Lower sodium pump activity has been reported in AA versus...

A Missing Link Between a High Salt Intake and Blood Pressure Increase

“…The prevalence of salt sensitivity (53.5% vs 51%) and salt resistance (25.3% vs 30.0%) in the participants was reported to be similar in African-American and white women (15). However, a greater mean BP increase with salt loading was seen in African-American vs white hypertensives, but not between the normotensive women.…”

“…However, a greater mean BP increase with salt loading was seen in African-American vs white hypertensives, but not between the normotensive women. In erythrocytes, [Na ] i were higher in African-Americans and were positively correlated with salt responsiveness, but this was not observed in white women (15). Sodium pump activity was similar in the white and black groups, although the changes in maximal activity tended to vary inversely with salt sensitivity in African-Americans (15).…”

A High-Density Admixture Scan in 1,670 African Americans with Hypertension

“…In future admixture mapping and whole genome scans for HTN genes in African Americans, it will be particularly important to study samples that have been assessed not only for presence or absence of HTN, but also for differences in covariates that are known to differ across populations such as plasma renin activity, urinary kallikrein, and dopamine levels [4]. This may also offer insights into the differences in blood pressure and salt handling known to exist between African and European Americans [15].…”

“…To date, four genome-wide admixture mapping scans have been published: one for HTN [11], one for multiple sclerosis [12], one for prostate cancer [13] and one for inflammatory biomarkers [14]. In addition to offering a novel method for identifying genetic determinants of HTN, admixture scans of HTN in African American may offer insights into the differences in salt-handling and blood pressure regulation between Africans/African Americans and European Americans; these differences are epidemiologically well-established and could be due to either genetic or non-genetic causes (see for example [15]). …”

Dietary Sodium and Blood Pressure

“…Wright et al examined ethnic differences in salt sensitivity in a study of 199 women. 3 In this crossover protocol, normotensive and hypertensive participants were given a low-salt (20 mEq/d) and high-salt (200 mEq/d) diet. The prevalence of salt sensitivity was similar in blacks and whites (just Ͼ50%), but the magnitude of blood pressure change was greater in the black women.…”