Erythrocyte aggregation, which plays an important role in the physiolo
gical behavior of blood fluidity, was found to be enhanced in hyperten
sion and hypercholesterolemia. While the role of macromolecule bridgin
g force has been widely described, cellular factors related to membran
e sialic acid content, which might contribute to the negative charge o
f cell surface causing the repulsion of erythrocytes, have been less s
tudied. Cell age-dependent changes in membrane sialic acid content (in
micromoles per gram of integral membrane protein) were investigated i
n 24 normotensive and 24 hypertensive matched subjects, each divided i
nto 2 identical subgroups according to a cutoff of 6.2 mmol/L serum ch
olesterol. A progressive and significant (P<0.001) decrease in membran
e sialic acid content associated with an increase (P<0.001) of disaggr
egation shear rate threshold (laser reflectometry in the presence of d
extran) were observed with increased erythrocyte density (erythrocytes
fractionated by density using ultracentrifugation) in both normotensi
ve and hypertensive groups regardless of the cholesterol level. Howeve
r, disaggregation shear rate threshold was significantly higher and si
alic acid content was lower (P<0.001) in both hypertensive and normote
nsive subjects with hypercholesterolemia compared with either normoten
sive or hypertensive subjects with low cholesterol, respectively. A hi
gh membrane sialic acid content variance, beginning in the younger ery
throcytes, was due mainly to triglyceride and LDL cholesterol levels (
R-2=0.49 for low, R-2=0.43 for middle, and R-2=0.54 for high densities
, ie, young, mean, and senescent erythrocytes, respectively). We concl
ude that an early decrease in erythrocyte sialic acid content may infl
uence the rheological properties of blood by increasing the adhesive e
nergy of erythrocyte aggregates.