Altered levels of erythrocyte calcium-binding proteins in essential hypertensives with genetic predisposition: correlation with ambulatory blood pressure.
OBJECTIVE
To examine whether changes in calcium-binding proteins, one of the components of the calcium ion handling mechanism, occur in humans with essential hypertension.


METHODS
We measured the levels of cytosolic calcium-binding proteins purified from human erythrocytes using a felodipine fluorescence assay, and examined the correlation between this parameter and the ambulatory blood pressure (ABP). We divided 127 subjects into four age-matched groups according to their mean ABP levels and whether they had a family history of both hypertension and stroke [group A hypertensives with a positive family history (n = 30), group B hypertensives with no family history (n = 31), group C normotensives with a family history (n = 31) and group D normotensives with no family history (n = 35) of hypertension and stroke].


RESULTS
The erythrocyte cytosolic level of calcium-binding proteins in group A was significantly lower than that in group B, as was that in group C compared with group D. There was no significant correlation between the erythrocyte level of calcium-binding proteins and casual blood pressure values in any group. However, in group A significant negative correlations between the erythrocyte level of calcium-binding proteins and systolic and mean ABP were observed (r = -0.34, P < 0.05 and r = -0.39, P < 0.05, respectively). No significant correlations between the ABP and erythrocyte levels of calcium-binding proteins were observed in the other groups. When each group was subdivided according to sex, there were significant negative correlations between the erythrocyte level of calcium-binding proteins and the systolic and mean ABP in the males of groups A and C, but no correlations were found in any of the female subgroups or the males of groups B and D. Reducing the blood pressure by antihypertensive drug therapy did not affect the erythrocyte calcium-binding proteins level in 13 patients from groups A and B. Analysis using anion-exchange fast-performance liquid chromatography on a Mono-Q column and sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed that the calcium-binding proteins in human erythrocytes, the levels of which were low in group A, formed a single protein band with a molecular weight of 17,000, which was assumed to be a calmodulin.


CONCLUSIONS
These results suggest that there are subgroups of hypertensive patients with low erythrocyte cytosolic levels of calcium-binding proteins, which are genetically determined. Furthermore, our data suggest that the erythrocyte level of calcium-binding proteins and ABP in male subjects with hypertension and normotensives with a genetic predisposition are correlated strongly, whereas no such correlation was observed in any female subgroup. This indicates that the regulatory mechanism or mechanisms involved in the control of blood pressure in men and women may be different.
Hojo
Y
Y
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Ebata
H
H
Kawasaki
K
K
Tsuruya
Y
Y
Ikeda
U
U
Nishinaga
M
M
Natsume
T
T
Ishida
H
H
Shimada
K
K
D000375:Aging / Q000097:blood; D000553:Ambulatory Care; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure; D001795:Blood Pressure Determination / Q000379:methods*; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000378:metabolism*; D015736:Felodipine / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D064030:S100 Calcium Binding Protein G / Q000097:blood* / Q000378:metabolism
D000959:Antihypertensive Agents; D064030:S100 Calcium Binding Protein G; D015736:Felodipine