Control of the Erythrocyte Free Ca Concentration in Essential Hypertension

Since Ca ions seem to directly participate in the control of erythrocyte membrane structure and deformability and because cell Ca metabolism has been repeatedly proposed to be modified in hypertension, the intracellular calcium ion concentration ([Ca],) was investigated in red blood cells from hypertensive and normotensive subjects. [Ca], was measured by using the fluorescent Ca chelator fura-2. Red blood cell [Ca], 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 [Ca], was observed when calculated with blood pressure adjusted. In hypertensive patients, high [Ca], values were associated with a reduced erythrocyte deformability. The initial rate of "Ca* uptake did not differ between the two blood pressure groups. Similarly, when the extracellular Ca concentration was elevated from 1 to 2 mmol/1, [Ca], increased by 16±4% (/?<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~ mol/1 nicardipine, a dihydropyridine Ca antagonist, decreased [Ca], by 15±4% (p<0.05) and 7±5% in erythrocytes from hypertensive and normotensive subjects, respectively, thereby reducing the difference in [Ca], observed between these two groups. This nicardipine effect was positively correlated to the initial [Ca],. In the presence of 5 /tmol/1 VV7, a calmodulin antagonist, [Ca], increased significantly only in erythrocytes from hypertensive patients (26±6%, p<0.01). These results demonstrate that essential hypertension is associated, in the erythrocyte, with an increased cytosolic Ca concentration, higher reduction of [Ca], by nicardipine, and an enhanced activity of the calmodulin-dependent regulatory mechanisms. {Hypertension 1992; 19:167-174)