Calmodulin Distribution and Ca2+ Transport in the Erythrocytes of Patients with Essential Hypertension

Abstract

The rate of calcium transport and calmodulin distribution in the erythrocytes of patients with essential hypertension were studied. In erythrocyte membranes subjected to calmodulin depletion by treatment with EGTA, both the affinity of the calcium pump for Ca2+ and its maximal activity were the same in normotensive and hypertensive patients. The addition of exogenous calmodulin to calmodulin-stripped membranes from erythrocytes of patients with essential hypertension resulted in a smaller increase of the maximal activity of the calcium pump and its affinity for Ca2+. The addition of calmodulin to erythrocyte membranes obtained without EGTA treatment resulted in a smaller increase of the maximal activity of the calcium pump only. There were no significant differences of calmodulin distribution (cytoplasmic concentration and size of the membrane-bound pool) between the erythrocytes of normotensive and hypertensive patients. It is suggested that alterations in the calcium pump activity of the erythrocyte membranes of patients with essential hypertension are related to the alteration of interaction between calmodulin and Mg2+, Ca2+-ATPase.

Decreased calcium pump adenosine triphosphatase in red blood cells of hypertensive subjects.

“…This supposition is consistent with the report of normal content and distribution of CaM in the RBCs of human hypertensive subjects. 24 As hypothesized by Postnov et al 24 the primary defect is related to the Ca 2+ that activates the ATPase in the absence of CaM. An alteration in membrane binding kinetics of Ca 2+ has been suggested, based on the reduced amount of exchangeable Ca 2+ available from isolated membranes of animals and humans with hypertension, 228 although total calcium of the membranes was reported to be increased.…”

“…30 It is conceivable that different amounts or effectiveness of CaM in normotensive versus hypertensive RBC lysates caused a difference in the basal Ca 2+ pump ATPase. Postnov et al 24 found no difference in the CaM content or cytoplasmic and membrane distribution between normotensive and hypertensive subjects. Nevertheless, it is possible that in the present study TFP distributed differently in the complicated lysate mixture of the two types of RBCs.…”

“…In platelets, a recent report demonstrated an increase in the intracellular concentration of Ca 2+ concurrent with a decrease in the extracellular concentration of the cation. 24 Extrapolation of our findings to vascular smooth muscle must be interpreted cautiously. The presence of the Ca 2+ pump ATPase has been demonstrated in smooth muscle, but the relationship of that pump and its regulation to the RBC is not well established.…”

An approach to the explanation of cell membrane alteration in primary hypertension.

“…20 The latter phenomenon was also observed in plasma membranes of cardiomyocytes and adipocytes of SHR, 13 and an increase of intracellular exchangeable calcium was revealed in adipose tissue in both types of primary hypertension. 27 At the same time, decreased activity of the calmodulin-dependent component of calcium pump activity was revealed in erythrocytes 28 and platelets 29 of EH patients and in erythrocytes, 30 synaptosomes, 25 and cardiomyocytes 31 of SHR. These studies were followed up by the finding of increased cytoplasmic free calcium concentration in platelets of both EH patients 32 The relation between alterations of cell calcium homeostasis and abnormalities in the transport systems of univalent cations in the plasma membrane is not always sufficiently clear.…”

Control of the erythrocyte free Ca2+ concentration in essential hypertension.

“…The basal activity was also found unchanged in EGTA-treated membranes, but its stimulation by calmodulin was reduced when compared with that of normotensive subjects. 12 - 16 Essential hypertension has been also reported to be associated with decreased 45 Ca 2+ uptake 17 and membrane Ca 2+ binding 1418 - 19 and increased or decreased total intracellular calcium content, measured by flame spectrometry or flameless atomic absorption. 20 - 21 Recently, the erythrocyte [Ca 2+ ]j, evaluated by nuclear magnetic resonance of a fluorinated derivative of quin-2 (2-[(2-bis[carboxymethyl]-amino-5-methylphenoxy)-methyl] -6 -methoxy-8 -bis [carboxymethyl] aminoquin-oline) or by fluorescence of fluo-3, was reported to be raised in hypertensive patients.…”