INTRACELLULAR IONIC CONSEQUENCES OF DIETARY SALT LOADING IN ESSENTIAL-HYPERTENSION - RELATION TO BLOOD-PRESSURE AND EFFECTS OF CALCIUM-CHANNEL BLOCKADE
Lm. Resnick et al., INTRACELLULAR IONIC CONSEQUENCES OF DIETARY SALT LOADING IN ESSENTIAL-HYPERTENSION - RELATION TO BLOOD-PRESSURE AND EFFECTS OF CALCIUM-CHANNEL BLOCKADE, The Journal of clinical investigation, 94(3), 1994, pp. 1269-1276
To study the ionic basis of salt sensitivity in hypertension, F-19-, (
31)p-, and Na-23-nuclear magnetic resonance techniques were used to me
asure 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 m
eq/d) and high- (UNaV > 200 meq/d) salt diets, with the concomitant ad
ministration 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 s
ubjects (n = 9). Nifedipine blunted the presser response to salt loadi
ng > 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 sal
t sensitivity, continuous relationships were observed between the pres
sure response to salt loading, the levels of Ca-i (r = 0.726, P < 0.00
1), Na-i (r = 0.747, P < 0.001), and pH(i) (r = -0.754, P < 0.001), an
d the salt-induced change in Mg-i (r = -0.757, P < 0.001). Altogether,
these results emphasize the reciprocal and coordinate nature of intra
cellular ionic changes in response to dietary salt loading and calcium
channel blockade in essential hypertension. They suggest that salt se
nsitivity is mediated by cellular calcium accumulation from the extrac
ellular space, in association with magnesium depletion and acidificati
on. Lastly, interpretation of intracellular ion measurements in the fu
ture will require concurrent assessment of dietary salt intake.