5-doxylstearate and Hypertension

It has been shown that rheological abnormality might be an etiological factor in hypertension. Recent studies have revealed that human erythrocytes possess a nitric oxide (NO) synthase and that this activation might be involved in the regulation of rheological properties of erythrocytes. The present study was undertaken to investigate the role of NO in the regulation of membrane functions of erythrocytes in patients with essential hypertension by means of an electron paramagnetic resonance (EPR) and spin-labeling method. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (h(0)/h(-1)) for 16-NS obtained from EPR spectra of erythrocyte membranes in a dose-dependent manner. The finding indicated that the NO donor increased the membrane fluidity of erythrocytes. In addition, the effect of SNAP was significantly potentiated by 8-bromo-cyclic guanosine monophosphate. By contrast, the change of the fluidity induced by SNAP was reversed in the presence of L-N(G)-nitroarginine methyl ester and asymmetric dimethyl L-arginine. In patients with essential hypertension, the membrane fluidity of erythrocytes was significantly lower than in the normotensive subjects. The effect of SNAP was more pronounced in essential hypertension than in normotensive subjects. These results showed that NO increased the membrane fluidity and decreased the rigidity of cell membranes. Furthermore, the greater effect of NO on the fluidity in essential hypertension suggests that NO might actively participate in the regulation of rheological behavior of erythrocytes and have a crucial role in the improvement of microcirculation in hypertension.

Topics: Arginine; Blood Pressure; Calcimycin; Cell Membrane; Cyclic GMP; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Erythrocytes; Hemorheology; Humans; Hypertension; Membrane Fluidity; Middle Aged; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Penicillamine; Spin Labels

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.

Topics: Adrenomedullin; Alprostadil; Bucladesine; Calcimycin; Calcium; Cyclic N-Oxides; Drug Combinations; Electron Spin Resonance Spectroscopy; Erythrocytes; Female; Humans; Hypertension; Male; Membrane Fluidity; Middle Aged; Peptides; Spin Labels; Vasodilator Agents

In the present study, we have examined the effects of ouabain on membrane fluidity of erythrocytes by use of an electron spin resonance (ESR) and spin-labeling method, and elucidated a possible role of Na+, K(+)-ATPase in the regulation of membrane fluidity in hypertension. Erythrocytes obtained from patients with essential hypertension were examined compared with those from age-matched normotensive subjects, and the ESR spectra for 5-nitroxy stearate incorporated into erythrocyte membranes were studied. The values of outer hyperfine splitting and order parameter (S) of the ESR spectra were significantly higher in patients with essential hypertension than in normotensive subjects. This finding shows that the membrane fluidity of erythrocytes might be lower in essential hypertension. Ouabain loading to erythrocytes decreased the membrane fluidity (S value was increased). The alternative degree was significantly greater in essential hypertension than in normotensive subjects. These results demonstrate that the membrane fluidity of erythrocytes might be highly dependent on the Na+, K(+)-ATPase activity in essential hypertension, which would suggest an abnormality in Na(+)-related cellular functions in hypertension.

Topics: Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Erythrocyte Membrane; Erythrocytes; Humans; Hypertension; Membrane Fluidity; Middle Aged; Ouabain; Sodium-Potassium-Exchanging ATPase