The effect of angiotensin II on platelet intracellular free magnesium and calcium ionic concentrations in essential hypertension


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Abstract

Objective:To assess the effects of angiotensin II on intracellular free Mg2+ and Ca2+ concentrations in platelets from normotensive and hypertensive subjects.Design and methods:Seventeen normotensive, 25 untreated hypertensive and 18 treated hypertensive patients were studied. Intracellular Mg2 + concentrations were measured with the fluorescent dye mag-fura-2-acetyoxymethylester (AM) and intracellular Ca2+ concentrations with the fluorescent dye fura-2AM under basal conditions and after stimulation by angiotensin II, saralasin (angiotensin II antagonist), arginine vasopressin and endothelin-1. The effects of increased extracellular Mg2 + concentrations on intracellular Mg2 + and Ca2+ concentrations were also determined.Results:The intracellular basal Ca2+ concentration was significantly higher in the untreated hypertensives compared with the normotensives and treated hypertensive subjects (150±14nmol/l versus 120±17nmol/l for normotensives and 124±8nmol/l for treated hypertensives). The basal intracellular Mg2 + concentration was significantly lower in the untreated hypertensive compared to the normotensive and treated hypertensive groups (0.37 ± 0.08 (imol/l versus 0.58 ± 0.09 u.mol/1 for normotensives and 0.52 ±0.11 u.mol/1 for treated hypertensives). In the hypertensive group, inverse correlations were found between intracellular Ca2+ and intracellular Mg2 + concentrations (r=-0.44, P < 0.05) and between intracellular Mg2 + and diastolic blood pressure (r=—0.35, P < 0.05), while a positive correlation was found between intracellular Ca2+ and systolic blood pressure (r=0.41, P < 0.05). Exposure of the platelets to 1 nmol/l angiotensin II significantly increased intracellular Ca2+ and significantly decreased intracellular Mg2 + concentrations in all three groups. The angiotensin ll-evoked effect on intracellular Ca2+ was exaggerated in the untreated hypertensives and blunted in the treated patients (basal versus stimulated: 150±14 versus 217±20nmol/l in untreated hypertensives; 124±8 versus 140±10nmol/l in treated hypertensives). Saralasin (0.1 u,mol/l) abolished the effects of angiotensin. Arginine vasopressin (1 u,mol/l) increased the intracellular Ca2+ concentration, whereas endothelin-1 (1 nmol/l) had no significant effect on either intracellular Ca2+ or intracellular Mg2 +. Increasing extracellular Mg2 + concentrations led to significant reductions in intracellular Ca2+ concentrations in all groups and a significant elevation of the intracellular Mg2 + concentration in the untreated hypertensive patients only.Conclusions:These data demonstrate a relationship between angiotensin II and intracellular magnesium and calcium. In hypertension, angiotensin ll-stimulated calcium responses may be related to simultaneously decreased intracellular magnesium concentrations.

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