Adrenomedullin and membrane fluidity of erythrocytes in mild essential hypertension

Abstract

Adrenomedullin is a newly discovered 52 amino acid peptide that has a potent vasodilating action. The present study was undertaken to investigate the role of adrenomedullin in the regulation of membrane fluidity of erythrocytes in patients with essential hypertension. We used an electron paramagnetic resonance and spin-labeling method. Adrenomedullin significantly decreased the order parameter for 5-nitroxide stearate and peak height ratio for 16-nitroxide stearate obtained from electron paramagnetic resonance spectra of erythrocyte membranes in normotensive volunteers (mean ± SEM order parameter value: control, 0.718 ± 0.003, n = 16; adrenomedullin at 10−9 mol/l, 0.692 ± 0.004, n = 16, P < 0.05; adrenomedullin at 10−8 mol/l, 0.690 ± 0.004, n = 16, P < 0.05; adrenomedullin at 10−7 mol/l, 0.683 ± 0.004, n = 16, P < 0.05). The findings showed that adrenomedullin increased the membrane fluidity of erythrocytes. In addition, the effect of adrenomedullin was significantly potentiated by prostaglandin E1 and dibutyryl cyclic AMP. In contrast, the calcium ionophore A23187 counteracted the actions of adrenomedullin. In patients with essential hypertension, who had higher order parameter values, the membrane fluidity of erythrocytes was significantly lower than in the normotensive control subjects (order parameter: 0.728 ± 0.004 in hypertensives, n = 20; 0.692 ± 0.002 in normotensives, n = 36, P < 0.01). The effect of adrenomedullin on membrane fluidity was more pronounced in the erythrocytes of essential hypertensive than in the erythrocytes of normotensive subjects (change in the order parameter with adrenomedullin at 10−9 mol/l:−4.2 ± 0.3% in hypertensives, n = 20; −1.8 ± 0.2% in normotensives, n = 20, P < 0.05; adrenomedullin at 10−8 mol/l: −4.5 ± 0.3% in hypertensives, n = 20; −1.8 ± 0.2% in normotensives, n = 36, P < 0.05). The results of the present study demonstrate that adrenomedullin significantly increased the membrane fluidity of erythrocytes. The mechanisms were partially mediated by a prostaglandin E1- and cyclic AMP-dependent pathway which might be linked to changes in intracellular calcium kinetics. The greater effect of adrenomedullin in patients with essential hypertension suggests that the peptide might actively participate in the regulation of membrane functions in hypertension.