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Elevated lymphocyte cytosolic calcium in a subgroup of essential hypertensive subjects
A Rivera1, P R Conlin, G H Williams
1Department of Medicine, Brigham and Women's Hospital, Boston, Mass. 02115, USA.
Insights
Essential hypertension is linked to abnormal calcium and sodium-proton exchange. Many hypertensive individuals show increased cytosolic calcium, but its link to sodium-proton exchange varies, suggesting complex salt-volume regulation issues.
Area of Science:
- Cardiovascular Physiology
- Cellular Biology
- Hypertension Research
Background:
- Essential hypertension is associated with dysregulated intracellular calcium homeostasis and sodium-proton exchange.
- Understanding the interplay between cytosolic calcium levels and sodium-proton exchange is crucial for elucidating hypertension pathophysiology.
Purpose of the Study:
- To investigate cytosolic calcium abnormalities in hypertensive versus normotensive individuals.
- To determine the relationship between elevated cytosolic calcium and sodium-proton exchange activity in hypertension.
- To explore the influence of salt intake on these cellular mechanisms.
Main Methods:
- Peripheral lymphocytes were analyzed from normotensive and hypertensive subjects under varying salt diets.
- Cytosolic calcium levels were measured, and maximum likelihood analysis identified distinct subgroups.
- Sodium-proton exchange activity was assessed in relation to calcium levels and salt balance.
Main Results:
- Hypertensive subjects exhibited significantly higher lymphocyte cytosolic calcium on a high-salt diet (P < .01).
- Analysis revealed three distinct cytosolic calcium level modes, with 120 nmol/L separating subgroups.
- Subjects with cytosolic calcium > 120 nmol/L (mostly hypertensive) showed no change with salt restriction but blood pressure fell; those < 120 nmol/L showed salt-dependent calcium changes and a correlation with sodium-proton exchange.
Conclusions:
- Increased cytosolic calcium is prevalent in hypertension but not uniformly linked to sodium-proton exchange activity.
- Salt-induced cytosolic calcium changes in some individuals suggest a role for salt-volume homeostasis factors.
- Hypertensive individuals with cytosolic calcium > 120 nmol/L may possess distinct regulatory abnormalities contributing to their condition.
Abstract:
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.