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Erythrocyte calcium-stimulated, magnesium-activated adenosine 5'-triphosphatase activity in essential hypertension
A S Adeoya1, R F Bing, R I Norman
1Department of Medicine, Leicester Royal Infirmary, UK.
Insights
Essential hypertension is linked to reduced erythrocyte calcium-stimulated, magnesium-activated adenosine 5' triphosphatase (Ca2+, Mg(2+)-ATPase) activity. This reduction stems from an altered membrane environment, not changes in enzyme properties.
Area of Science:
- Biochemistry
- Cardiovascular Physiology
- Cell Biology
Background:
- Essential hypertension is a prevalent cardiovascular condition.
- Erythrocyte Ca2+, Mg(2+)-ATPase activity is crucial for calcium homeostasis.
- Reduced enzyme activity has been observed in hypertensive individuals.
Purpose of the Study:
- To investigate the underlying causes of diminished erythrocyte Ca2+, Mg(2+)-ATPase activity in essential hypertension.
- To differentiate between alterations in enzyme properties and changes in the erythrocyte membrane environment.
Main Methods:
- Erythrocyte membrane Ca2+, Mg(2+)-ATPase activity was assessed using ATP-dependent 45Ca2+ uptake and calcium-dependent gamma-32P ATP hydrolysis assays.
- Experiments were conducted on inside-out vesicles, ghost membranes, and detergent extracts of erythrocyte membranes.
- Comparisons were made between patients with essential hypertension and age- and sex-matched normotensive control subjects.
Main Results:
- Erythrocyte membranes from hypertensive patients showed significantly reduced ATP-dependent Ca2+ uptake and calcium-dependent ATP hydrolysis compared to normotensive controls.
- Calmodulin affinity was similar between groups, but calmodulin-independent Ca2+ uptake showed altered calcium dependence in hypertensive subjects.
- Detergent solubilization eliminated differences in calcium-dependent ATP hydrolysis activity, suggesting the enzyme itself was not fundamentally altered.
Conclusions:
- The number of Ca2+, Mg(2+)-ATPase units appears consistent between hypertensive and normotensive erythrocytes.
- The observed reduction in Ca2+, Mg(2+)-ATPase activity in intact erythrocyte membranes of hypertensive patients is attributed to modifications within the membrane environment.
- These findings highlight the role of the erythrocyte membrane in the pathophysiology of essential hypertension.
Objective:
The aim of this study was to investigate the basis of reduced erythrocyte calcium-stimulated, magnesium-activated adenosine 5' triphosphatase (Ca2+, Mg(2+)-ATPase) activity in essential hypertension.
Design:
Experiments were performed to establish whether the reduced erythrocyte Ca2+, Mg(2+)-ATPase activity in patients with essential hypertension, when compared with age- and sex-matched normotensive control subjects, was due to changes in enzyme properties or to an altered membrane environment.
Methods:
Erythrocyte membrane Ca2+, Mg(2+)-ATPase activity was determined by measuring ATP-dependent 45Ca2+ uptake in inside-out vesicles and calcium-dependent gamma-32P ATP hydrolysis in ghost membranes, prepared from the same sample of blood. Calcium-dependent gamma-32P ATP hydrolysis activity was also measured in detergent extracts of erythrocyte membranes.
Results:
In the absence and presence of calmodulin, both ATP-dependent Ca2+ uptake and calcium-dependent ATP hydrolysis activities of erythrocyte membranes prepared from patients with essential hypertension were significantly reduced when compared with normotensive subjects. No difference in calmodulin affinity was observed between hypertensive and normotensive subjects, although the calcium dependence of calmodulin-independent Ca2+ uptake activity in inside-out vesicles was altered. No significant difference in calcium-dependent ATP hydrolysis activity was observed between hypertensive and normotensive preparations after detergent solubilization of erythrocyte membrane proteins.
Conclusions:
These results suggest that the number of Ca2+, Mg(2+)-ATPase units is similar in erythrocytes of hypertensive and normotensive subjects and that the reduced activity in the intact erythrocyte membrane of hypertensive patients is due to an altered membrane environment.