Abnormalities of intracellular calcium homeostasis and sodium-proton e
xchange have been implicated in the pathophysiology of essential hyper
tension. To further define the nature of cytosolic calcium abnormaliti
es and whether they relate to increased sodium-proton exchange in hype
rtension, we have studied peripheral lymphocytes from normotensive and
hypertensive subjects. Lymphocyte cytosolic calcium was significantly
increased (P <.01) in hypertensive compared with normotensive subject
s while consuming a high salt diet. Using maximum likelihood analysis,
we found that cytosolic calcium levels in our study population were n
ot normally distributed and observed three modes (P <.02). The means o
f the first mode and the two upper modes were separated (+/-2 SD) at a
cytosolic calcium level of 120 nmol/L. We conducted further analysis
in the subgroups with cytosolic calcium levels >120 nmol/L or <120 nmo
l/L. The majority of the normotensive subjects (86%) and half of the h
ypertensive subjects (52%) had levels <120 nmol/L. Clinical characteri
stics of the two subgroups did not differ. Subjects with levels <120 n
mol/L had a rise in cytosolic calcium when changed to a low salt diet;
those with levels >120 nmol/L did not show a change in cytosolic calc
ium but their blood pressure fell significantly with salt restriction.
Hypertensive subjects also had increased sodium-proton exchange activ
ity compared with normotensive subjects when both groups were studied
in a high salt balance. A positive correlation between sodium-proton e
xchange and cytosolic calcium was observed in subjects with levels <12
0 nmol/L. There was insufficient power to draw conclusions on this rel
ationship in subjects with levels >120 nmol/L. Thus, many hypertensive
subjects have increased cytosolic calcium, but this abnormality is no
t associated with sodium-proton exchange activity in all individuals.
The salt-induced change in cytosolic calcium in subjects with levels <
120 nmol/L and its link to sodium-proton exchange suggest regulation b
y factors involved in salt-volume homeostasis. Individuals with cytoso
lic calcium >120 nmol/L, most of whom were hypertensive, may have abno
rmalities in this regulation, contributing to hypertension.