Platelet calcium transport in hypertension.
To determine platelet Ca2+ transport entities involved in increased cytosolic Ca2+ in the platelets of hypertensive individuals, we studied the relations between blood pressure and Ca2+ transporters in platelet membranes from 22 white male volunteers 32 to 68 years old. We used thapsigargin, a specific inhibitor of the internal membrane Ca(2+)-ATPase, to differentiate between plasma membrane and internal membrane Ca(2+)-ATPases. Inositol 1,4,5-trisphosphate-mediated and Ca2+ ionophore (A23187)-induced Ca2+ release was also assayed in membrane preparations using rhod-2, a fluorescent Ca2+ indicator. Levels of glycoprotein IIIa, a possible component of agonist-mediated Ca2+ influx, were measured by immunoblotting. The results show that plasma membrane Ca(2+)-ATPase is decreased as a function of diastolic blood pressure (P < .002), whereas the internal membrane Ca(2+)-ATPase is not (P < .148). Neither activity is correlated with age or systolic blood pressure. However, inositol trisphosphate-mediated Ca2+ release is negatively correlated with age (P < .024) but not blood pressure. Glycoprotein IIIa levels and A23187-induced Ca2+ release were not related to age or blood pressure, demonstrating that inhibition of the plasma membrane Ca(2+)-ATPase was not a result of differences in the proportion of plasma membrane in the preparation or differences in intravesicular Ca2+ concentration. Inhibition of the plasma membrane Ca(2+)-ATPase could directly cause elevation of cytoplasmic Ca2+ and enhancement of platelet sensitivity.
Dean
W L
WL
Department of Biochemistry, University of Louisville School of Medicine, KY 40292.
Pope
J E
JE
Brier
M E
ME
Aronoff
G R
GR
D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism*; D017136:Ion Transport; D008297:Male; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins / Q000032:analysis
D010980:Platelet Membrane Glycoproteins; D000252:Calcium-Transporting ATPases; D002118:Calcium