INTRACELLULAR IONIC CONSEQUENCES OF DIETARY SALT LOADING IN ESSENTIAL-HYPERTENSION - RELATION TO BLOOD-PRESSURE AND EFFECTS OF CALCIUM-CHANNEL BLOCKADE

To study the ionic basis of salt sensitivity in hypertension, F-19-, (31)p-, and Na-23-nuclear magnetic resonance techniques were used to measure cytosolic free calcium (Ca-i), pH (pH(i)), free magnesium (Mg-i), and sodium (Na-i) 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 Ca-i and Na-i while suppressing Mg-i and pH(i); these changes occurred predominantly in salt-sensitive subjects (n = 9). Nifedipine blunted the presser response to salt loading > 50% (Delta diastolic BP [high-low salt vs placebo] = 5+/-2 vs 14+/-2 mmHg, P < 0.05) and reversed salt-induced ionic changes, lowering Ca-i and elevating Mg-i and pH(i). Regardless of the definition of salt sensitivity, continuous relationships were observed between the pressure response to salt loading, the levels of Ca-i (r = 0.726, P < 0.001), Na-i (r = 0.747, P < 0.001), and pH(i) (r = -0.754, P < 0.001), and the salt-induced change in Mg-i (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.