To study the ionic basis of salt sensitivity in hypertension, Tl_-, 31p-, and 'Na-nuclear magnetic resonance techniques were used to measure cytosolic free calcium (Ca1), pH (pH,), free magnesium (Mg1), and sodium (Na4) in erythrocytes of essential hypertensive subjects (n = 19). Individuals were studied for 2 mo each on low-(UNaV < 50 meq/d) and high-(UNaV > 200 meq/d) salt diets, with the concomitant administration of nifedipine (10 mg t i.d.) or placebo tablets for 1 mo of each diet. Salt loading elevated Ca1 and Na1 while suppressing Mg, and pH,; these changes occurred predominantly in salt-sensitive subjects (n = 9). Nifedipine blunted the pressor response to salt loading > 50% (A diastolic BP [high-low salt vs placebo] = 5±2 vs 14±2 mmHg, P < 0.05) and reversed salt-induced ionic changes, lowering Cal and elevating Mg& and pHi. Regardless of the definition of salt sensitivity, continuous relationships were observed between the pressure response to salt loading, the levels of Ca1 (r = 0.726, P < 0.001), Nai (r = 0.747, P < 0.001), and pH1 (r = -0.754, P < 0.001), and the salt-induced change in Mg& (r = -0.757, P < 0.001). Altogether, these results emphasize the reciprocal and coordinate nature of intracellular ionic changes in response to dietary salt loading and calcium channel blockade in essential hypertension. They suggest that salt sensitivity is mediated by cellular calcium accumulation from the extracellular space, in association with magnesium depletion and acidification. Lastly, interpretation of intracellular ion measurements in the future will require concurrent assessment of dietary salt intake. (J. Clin. Invest. 1994. 94:1269-1276

This study examined the effect of large changes in dietary sodium on the average ambulatory blood pressure and its variability in 19 patients with uncomplicated borderline hypertension. Each patient participated in a 16-week protocol that consisted of four 4-week periods of different sodium intake (medium (120-160 mEq/day) during periods 1 and 3 and low (< 40 mEq/day) or high (> 225 mEq/day) during either period 2 or 4. The 24-hour urine sodium during the low and high periods averaged 18 and 327 mEq/day, respectively. Ambulatory blood pressure monitoring was done at the end of the fourth week of the low and high diet periods. During monitoring, pressures were recorded every 15 minutes while awake; in addition, patients kept diaries noting activities, posture, and situation at each measurement. The results show that there was a decline of 16/7 mmHg in the average ambulatory awake systolic and diastolic pressures from the high sodium to low sodium diets. Corresponding casual pressures decreased an average of 15 and 8 mmHg, respectively. In examining the factors associated with ambulatory pressure variability, systolic pressure showed greater variation by activity on a low sodium diet than on the high. The findings suggest that sodium restriction has a variable, but in some cases marked, effect on lowering the ambulatory blood pressure in borderline mildly hypertensive patients and that sodium balance may be important to consider when examining ambulatory blood pressure variability. © 1994 Wiley-Liss, Inc.