Erythrocytes In Essential Hypertension Research Articles

P-382 Benidipine, a Long-Acting Calcium Channel Blocker, Improves Membrane Fluidity of Erythrocytes in Essential Hypertension

P-382 Benidipine, a Long-Acting Calcium Channel Blocker, Improves Membrane Fluidity of Erythrocytes in Essential Hypertension

Electron paramagnetic resonance investigation on modulatory effect of benidipine on membrane fluidity of erythrocytes in essential hypertension

It has been shown that benidipine, a long-lasting calcium (Ca) channel blocker, may exert its protective effect against vascular disorders by increasing nitric oxide (NO) production. The purpose of the present study was to investigate whether orally administered benidipine might influence the membrane function in patients with essential hypertension. We measured the membrane fluidity of erythrocytes by using an electron paramagnetic resonance (EPR) and spin-labeling method. In the preliminary study using erythrocytes obtained from healthy volunteers, benidipine decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS in the EPR spectra in vitro. The finding indicated that benidipine increased the membrane fluidity and improved the microviscosity of erythrocytes. In addition, it was demonstrated that the effect of benidipine on membrane fluidity of erythrocytes was significantly potentiated by the NO-substrate, L-arginine. In the separate series of the study, we observed that orally administered benidipine for 4 weeks significantly increased the membrane fluidity of erythrocytes with a concomitant increase in plasma NO metabolite levels in hypertensive subjects. The results of the present study demonstrated that benidipine might increase the membrane fluidity and improve the microviscosity of erythrocytes both in vitro and in vivo, to some extent, by the NO-dependent mechanism. Furthermore, it is strongly suggested that orally administered benidipine might have a beneficial effect on the rheologic behavior of erythrocytes and the improvement of the microcirculation in hypertensive subjects.

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Leptin and membrane fluidity of erythrocytes in essential hypertension: an electron paramagnetic resonance investigation

There has been an indication that leptin, the product of the human obesity gene, actively participates not only in metabolic regulation but also in the control of blood pressure. Recently, it has been proposed that abnormalities in the physical property of cell membranes may underlie the defects that are strongly linked to hypertension, stroke, and other cardiovascular diseases. We have shown previously that leptin significantly increased the membrane fluidity and improved the microviscosity of erythrocytes in humans through the nitric oxide-dependent mechanism. In the present study, we examined the effects of leptin on membrane fluidity of erythrocytes in subjects with essential hypertension by means of an electron paramagnetic resonance (EPR) and spin-labeling method. The values of the order parameter (S) and the peak height ratio (ho/h-1) obtained from the EPR spectra of erythrocytes were significantly greater in patients with essential hypertension (HT) than in age-matched normotensive subjects (NT) (S: HT 0.719 ± 0.002, n = 16, NT 0.713 ± 0.001, n = 29, P < .05; ho/h-1: HT 5.17 ± 0.02, n = 16, NT 5.05 ± 0.02, n = 29, P < .05). The finding indicated that the erythrocyte membrane fluidity was lower in patients with HT than in NT. Leptin decreased S and ho/h-1 in a dose-dependent manner in both NTs and HTs. The effect of leptin on the membrane fluidity was significantly more pronounced in HTs than in NTs (percent change in S: leptin 10 −8 g/mL, HT −3.4% ± 0.2%, n = 16, NT −2.3% ± 0.1%, n = 29, P < .05; leptin 10 −7 g/mL, HT −4.3% ± 0.3%, n = 16, NT −3.3% ± 0.1%, n = 29, P < .05). The results of the present study showed that leptin might have a crucial role in the regulation of the rheologic behavior of erythrocytes and the microcirculation in hypertension.

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Hyperinsulinemia and membrane fluidity: Hyperinsulinemia is a determinant of membrane fluidity of erythrocytes in essential hypertension

In the present study, to determine a possible role of insulin in the regulation of membrane functions, we have examined the relationship between plasma insulin level and membrane fluidity of erythrocytes in patients with essential hypertension and normotensive subjects. Membrane fluidity of erythrocytes obtained from hypertensive and normotensive subjects were evaluated by means of an electron paramagnetic resonance and spin-labeling method. The order parameter (S for 5-nitroxide stearate) and the peak height ratio (ho/h-1 for 16-nitroxide stearate) obtained from electron paramagnetic resonance spectra of erythrocyte membranes were significantly higher in patients with essential hypertension than in normotensive subjects. The finding indicated that the erythrocyte membrane fluidity was lower in essential hypertension than in normotensive controls. The plasma concentration of insulin while fasting was also significantly greater in hypertensive patients than in normotensive subjects. In addition, the plasma insulin level was significantly correlated with the values of the order parameter (S) and the peak height ratio (ho/h-1), which showed that the higher plasma insulin was associated with the lower membrane fluidity of erythrocytes. These results support the hypothesis that insulin may actively participate in the regulation of membrane fluidity of erythrocytes in essential hypertension.

Nitric Oxide Improves Membrane Fluidity of Erythrocytes in Essential Hypertension: An Electron Paramagnetic Resonance Investigation

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 (h0/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-NG-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.

Role of insulin in the regulation of membrane fluidity of erythrocytes in essential hypertension: an electron paramagnetic resonance investigation

In the present study, to determine a possible role of insulin in the regulation of membrane functions, we have examined the effects of insulin on the membrane fluidity of erythrocytes in patients with essential hypertension and normotensive subjects. Membrane fluidity of erythrocytes obtained from hypertensive and normotensive subjects were evaluated by means of an electron paramagnetic resonance (EPR) and a spin-labeling method. In an in vitro study, insulin increased the order parameter (S for 5-nitroxide stearate) and the peak height ratio (ho/h-1 for 16 nitroxide stearate) in the EPR spectra of erythrocyte membranes, which indicated that insulin decreased the membrane fluidity of erythrocytes. The effects of insulin on the membrane fluidity were potentiated in the presence of extracellular Ca 2 + , and in contrast, were antagonized by the Ca 2 + channel blocker diltiazem. Furthermore, the effects of insulin alone and in combination with Ca 2 + on the membrane fluidity were reduced in the erythrocytes from hypertensive subjects compared with the erythrocytes from normotensive controls. The high concentrations of glucose alone produced no significant effects on the membrane fluidity of erythrocytes. These results demonstrated that insulin might actively participate in the regulation of membrane fluidity of erythrocytes, which might be mediated by the intracellular Ca 2 + kinetics.

Insulin and membrane function of erythrocytes in essential hypertension -an electron paramagnetic resonance investigation-

Insulin and membrane function of erythrocytes in essential hypertension -an electron paramagnetic resonance investigation-

Membrane fluidity of erythrocytes and its modulation by ouabain in essential hypertension--an electron paramagnetic resonance study.

The purpose of the present study was to examine alterations in membrane fluidity of erythrocytes in essential hypertension by means of an electron paramagnetic resonance (EPR) and a spin labeling method. In addition, we investigated the effects of ouabain on the fluidity of erythrocytes, 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. The EPR spectra for 5-nitroxide stearate incorporated into erythrocyte membranes were studied. The values of the outer hyperfine splitting and order parameter (S) of the EPR 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 of erythrocytes decreased the membrane fluidity (S value was increased). The ouabain-induced changes were significantly greater in essential hypertension than in normotensive subjects. These results demonstrate that the membrane fluidity of erythrocytes might be lower in essential hypertension than in normotensive subjects. Furthermore, the membrane fluidity 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.

The role of endogenous Na+,K+-adenosine triphosphatase inhibitory factor in the regulation of membrane fluidity of erythrocytes in essential hypertension

To investigate the regulatory mechanisms of membrane functions in hypertension, we examined the relationship between endogenous Na+, K(+)-adenosine triphosphatase (ATPase) inhibitor (digitalis-like factor; DLF) and erythrocyte membrane fluidity in essential hypertension by means of an electron spin resonance (ESR) and spin labelling methods. Erythrocytes were obtained from patients with essential hypertension and normotensive subjects, and the ESR spectra for a fatty acid spin label agent (5-nitroxide stearate) incorporated into the erythrocyte membranes were studied. The DLF content in plasma was expressed as the inhibitory potency of dog kidney Na+, K(+)-ATPase activity in vitro. The values of outer hyperfine splitting and of order parameter in ESR spectra were significantly higher in hypertensive patients than in normotensive subjects. This finding shows that the erythrocyte membrane fluidity may be decreased in essential hypertension. The level of plasma DLF content was greater in hypertensive patients than in normotensive subjects and was significantly correlated with the decrease in erythrocyte membrane fluidity. These results suggest that the decrease in erythrocyte membrane fluidity may be partially dependent upon the increased plasma DLF content.

Effects of ouabain on membrane fluidity of erythrocytes in essential hypertension. An electron spin resonance study.

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.

Age-related Changes in Membrane Fluidity of Erythrocytes in Essential Hypertension

In the present study, age- and calcium-related changes in the membrane fluidity of erythrocytes were examined in patients with essential hypertension by use of electron spin resonance method (ESR). The erythrocytes were obtained from patients with essential hypertension. We examined the ESR spectra for a fatty acid spin label agent (5-nitroxy stearate) incorporated into the erythrocyte membranes. The values of outer hyperfine splitting and order parameter (S) were significantly higher in subjects with essential hypertension than in the normotensive subjects. This finding indicates that the membrane fluidity of erythrocytes was lower in essential hypertension. Calcium-loading of erythrocytes with the Ca-ionophore A23187 decreased the membrane fluidity (S value was increased) more strongly in essential hypertension than in the normotensive subjects. Furthermore, this Ca-induced change in membrane fluidity was significantly correlated with age in essential hypertension. These results demonstrate that the membrane fluidity of erythrocytes is markedly decreased by calcium, especially in essential hypertension in older patients. This suggests an increased calcium-sensitivity of cell membranes in the aged hypertensive patient.

Decreased water and potassium content in erythrocytes in essential hypertension.

The water content in erythrocytes of subjects with borderline or established essential hypertension was measured by using gas-liquid chromatography and was found to be lower than that in normotensive controls (p less than 0.01). The water content in erythrocytes of normal controls (n = 14), borderline hypertensive subjects (n = 18), and established essential hypertensive subjects (n = 23) was (mean +/- SE) 71.0 +/- 0.2%, 69.9 +/- 0.2%, and 69.3 +/- 0.1% (vol/vol), respectively. A definite negative correlation was found between water content of erythrocytes and mean arterial pressure in normotensive and hypertensive subjects (n = 60, r = -0.59, p less than 0.001). Although there was no statistically significant between-group difference in the sodium content, the potassium content of erythrocytes from subjects with essential hypertension was significantly lower than that of normotensive controls (0.205 +/- 0.003 vs 0.222 +/- 0.004 mumol/mg dry red blood cells; p less than 0.01). There was no between-group correlation of sodium and water content in erythrocytes, but the potassium content correlated with the water content (n = 46, r = 0.49, p less than 0.001).

本態性高血圧および高血圧自然発症ラットにおける細胞膜Ca-handlingの異常について

本態性高血圧および高血圧自然発症ラットにおける細胞膜Ca-handlingの異常について

Increased Sodium Influx into Erythrocytes in Diabetes Mellitus and Hypertension

A variety of abnormality has been reported in the cation transport systems in erythrocytes in essential hypertension. To determine the existence of similar abnormality in diabetics with hypertension, sodium (Na+) influx into erythrocytes in the presence of ouabain (measured by using 22Na+), and the Na+ and potassium (K+) content in intact erythrocytes were examined. Subjects, all of whom were Japanese, were divided into 4 groups; 23 nondiabetic, normotensive control subjects without family history of hypertension (control group), 20 patients with essential hypertension (group 1), 21 normotensive diabetics without family history of hypertension (group 2) and 15 hypertensive diabetics (group 3). Na+-K+ pump activity (measured by using 86Rb+) was studied in some of them, too. Na+ influx in group 1 was 0.451 +/- 0.111 m mol/Kg erythrocytes/h, significantly more elevated than that in the control group (0.345 +/- 0.080, p less than 0.001). Na+ influx in group 2 (0.435 +/- 0.094) was significantly greater than that in the control group (p less than 0.005), but no significant difference was found between groups 1 and 2. Na+ influx in group 3 (0.551 +/- 0.128) was significantly higher than that in the control group (p less than 0.001), in group 1 (p less than 0.02), or in group 2 (p less than 0.005). There were no significant differences in Na+-K+ pump activity, or Na+ and K+ content among the 4 groups. These findings suggested that: Na+ influx into ouabain-treated erythrocytes was higher in patients with essential hypertension than in control subjects in Japanese, diabetes mellitus per se might increase Na+ influx, and the elevation of blood pressure in hypertensive diabetics as well as in essential hypertensives might be related to the increased Na+ influx.

Potassium Influx into Erythrocytes in Essential Hypertension

Sodium plus potassium (Na + K) cotransport in erythrocytes of patients with essential hypertension has mainly been studied elsewhere by measuring net outward frusemide-sensitive Na and K movements. We compared K influx (tracer86 Rubidium) in control subjects and hypertensives who had never previously been treated for hypertension. The cotransport K influx rates in controls and hypertensives were 0.44 ± 0.02 (μmol/ml cells/h; mean ± s.e.; n = 20) and 0.67 ± 0.06 (μmol/ml cells/h; mean ± s.e; n = 23) respectively. The active influxes were 1.03 ± 0.03 and 2.06 ± 0.13 (μmol/ml cells/h; mean ± s.e.) respectively. The variance of both parameters was significantly greater in the hypertensive group but, taking this into account, the differences were significant (P < 0.01). Journal of Hypertension 2:405-409, 1984

Potassium Influx into Erythrocytes in Essential Hypertension

Sodium plus potassium (Na+K) cotransport in erythrocytes of patients with essential hypertension has mainly been studied elsewhere by measuring net outward frusemide-sensitive Na and K movements. We compared K influx (tracer 86 Rubidium) in control subjects and hypertensives who had never previously been treated for hypertension. The cotransport K influx rates in controls and hypertensives were 0.44 +/- 0.02 (mumol/ml cells/h; mean +/- s.e.; n = 20) and 0.67 +/- 0.06 (mumol/ml cells/h; mean +/- s.e.; n = 23) respectively. The active influxes were 1.03 +/- 0.03 and 2.06 +/- 0.13 (mumol/ml cells/h; mean +/- s.e.) respectively. The variance of both parameters was significantly greater in the hypertensive group but, taking this into account, the differences were significant (P less than 0.01).

Changes in Two Sodium Transports in Erythrocytes in Essential Hypertension: Their Relationship to Each other and to the Family History

Conference Abstract| September 01 1982 Changes in Two Sodium Transports in Erythrocytes in Essential Hypertension: Their Relationship to Each other and to the Family History C. Clegc; C. Clegc 1Department of Chemical Pathology, University of Leeds and Birch Hill Hospital, Rochdale, Lancs Search for other works by this author on: This Site PubMed Google Scholar C. Davidson; C. Davidson 1Department of Chemical Pathology, University of Leeds and Birch Hill Hospital, Rochdale, Lancs Search for other works by this author on: This Site PubMed Google Scholar D.B. Morgan D.B. Morgan 1Department of Chemical Pathology, University of Leeds and Birch Hill Hospital, Rochdale, Lancs Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1982) 63 (3): 30P–31P. https://doi.org/10.1042/cs063030Pb Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation C. Clegc, C. Davidson, D.B. Morgan; Changes in Two Sodium Transports in Erythrocytes in Essential Hypertension: Their Relationship to Each other and to the Family History. Clin Sci (Lond) 1 September 1982; 63 (3): 30P–31P. doi: https://doi.org/10.1042/cs063030Pb Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search nav search search input Search input auto suggest search filter All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1982 The Biochemical Society and the Medical Research Society1982 Article PDF first page preview Close Modal You do not currently have access to this content.

Changes in binding of calcium ions and in function of Na+, K+-ATPase in the erythrocytes in essential hypertension

More calcium was removed by EDTA from the membranes of erythrocytes of patients with hypertension than from the erythrocytes of persons with a normal blood pressure. By the use of an isotonic solution of MgCl2, the quantity of calcium removed from the erythrocyte membrane was the same in both groups. Activity of Na, K-ATPase in the membrane of reconstituted erythrocytes of patients with essential hypertension increased its activity in healthy human erythrocytes.