Control of the erythrocyte free Ca2+ concentration in essential hypertension.
Since Ca2+ ions seem to directly participate in the control of erythrocyte membrane structure and deformability and because cell Ca2+ metabolism has been repeatedly proposed to be modified in hypertension, the intracellular calcium ion concentration ([Ca2+]i) was investigated in red blood cells from hypertensive and normotensive subjects. [Ca2+]i was measured by using the fluorescent Ca2+ chelator fura-2. Red blood cell [Ca2+]i was increased in hypertensive compared with normotensive subjects in the whole population and further increased when hypertensive were compared with age-matched normotensive subjects. An inverse relation between age and [Ca2+]i was observed when calculated with blood pressure adjusted. In hypertensive patients, high [Ca2+]i values were associated with a reduced erythrocyte deformability. The initial rate of 45Ca2+ uptake did not differ between the two blood pressure groups. Similarly, when the extracellular Ca2+ concentration was elevated from 1 to 2 mmol/l, [Ca2+]i increased by 16 +/- 4% (p less than 0.03) in red blood cells from both groups, thus maintaining a significant difference between hypertensive and normotensive subjects. Under these conditions, the addition of 10(-7) mol/l nicardipine, a dihydropyridine Ca2+ antagonist, decreased [Ca2+]i by 15 +/- 4% (p less than 0.05) and 7 +/- 5% in erythrocytes from hypertensive and normotensive subjects, respectively, thereby reducing the difference in [Ca2+]i observed between these two groups. This nicardipine effect was positively correlated to the initial [Ca2+]i. In the presence of 5 mumol/l W7, a calmodulin antagonist, [Ca2+]i increased significantly only in erythrocytes from hypertensive patients (26 +/- 6%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
David-Dufilho
M
M
Department of Pharmacology, CNRS 16167, Necker Medical School, Paris, France.
Astarie
C
C
Pernollet
M G
MG
Del Pino
M
M
Levenson
J
J
Simon
A
A
Devynck
M A
MA
D002118:Calcium / Q000097:blood*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012016:Reference Values; D012212:Rheology; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D013449:Sulfonamides; C017967:W 7; D002118:Calcium