ALTERED LEVELS OF ERYTHROCYTE CALCIUM-BINDING PROTEINS IN ESSENTIAL HYPERTENSIVES WITH GENETIC PREDISPOSITION - CORRELATION WITH AMBULATORYBLOOD-PRESSURE

Objective: To examine whether changes in calcium-binding proteins, one of the components of the calcium ion handling mechanism, occur in hum ans with essential hypertension. Design: We measured the levels of cyt osolic 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 12 7 subjects into four age-matched groups according to their mean ABP le vels and whether they had a family history of both hypertension and st roke [group A hypertensives with a positive family history (n = 30), g roup B hypertensives with no family history (n=31), group C normotensi ves with a family history (n=31) and group D normotensives with no fam ily history (n=35) of hypertension and stroke]. Results: The erythrocy te cytosolic level of calcium-binding proteins in group A was signific antly 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 betw een 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, respecti vely). No significant correlations between the ABP and erythrocyte lev els of calcium-binding proteins were observed in the other groups. Whe n each group was subdivided according to sex, there were significant n egative 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 antihypertensi ve drug therapy did not affect the erythrocyte calcium-binding protein s level in 13 patients from groups A and B. Analysis using anion-excha nge fast-performance liquid chromatography on a Mono-Q column and sodi um dodecyl sulphate-polyacrylamide gel electrophoresis revealed that t he calcium-binding proteins in human erythrocytes, the levels of which were low in group A, formed a single protein band with a molecular we ight of 17 000, which was assumed to be a calmodulin. Conclusions: The se results suggest that there are subgroups of hypertensive patients w ith low erythrocyte cytosolic levels of calcium-binding proteins, whic h are genetically determined. Furthermore, our data suggest that the e rythrocyte 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 f emale subgroup. This indicates that the regulatory mechanism or mechan isms involved in the control of blood pressure in men and women may be different.