Elevated lymphocyte cytosolic calcium in a subgroup of essential hypertensive subjects.
Abnormalities of intracellular calcium homeostasis and sodium-proton exchange have been implicated in the pathophysiology of essential hypertension. To further define the nature of cytosolic calcium abnormalities and whether they relate to increased sodium-proton exchange in hypertension, we have studied peripheral lymphocytes from normotensive and hypertensive subjects. Lymphocyte cytosolic calcium was significantly increased (P < .01) in hypertensive compared with normotensive subjects while consuming a high salt diet. Using maximum likelihood analysis, we found that cytosolic calcium levels in our study population were not normally distributed and observed three modes (P < .02). The means of 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 nmol/L. The majority of the normotensive subjects (86%) and half of the hypertensive subjects (52%) had levels < 120 nmol/L. Clinical characteristics of the two subgroups did not differ. Subjects with levels < 120 nmol/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 calcium but their blood pressure fell significantly with salt restriction. Hypertensive subjects also had increased sodium-proton exchange activity compared with normotensive subjects when both groups were studied in a high salt balance. A positive correlation between sodium-proton exchange and cytosolic calcium was observed in subjects with levels < 120 nmol/L. There was insufficient power to draw conclusions on this relationship in subjects with levels > 120 nmol/L. Thus, many hypertensive subjects have increased cytosolic calcium, but this abnormality is not 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 by factors involved in salt-volume homeostasis. Individuals with cytosolic calcium > 120 nmol/L, most of whom were hypertensive, may have abnormalities in this regulation, contributing to hypertension.
Rivera
A
A
Department of Medicine, Brigham and Women's Hospital, Boston, Mass. 02115, USA.
Conlin
P R
PR
Williams
G H
GH
Canessa
M L
ML
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012982:Sodium, Dietary / Q000378:metabolism / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D012982:Sodium, Dietary; D017923:Sodium-Hydrogen Exchangers; D002118:Calcium