Kazushi Tsuda

Bone mineral density in women with essential hypertension

Recent studies have reported the abnormalities in calcium metabolism at the systemic level in human hypertension as well as in experimental hypertension. Because bone is the largest store of calcium in the body, the bone calcium content and mineralization may represent the entire calcium balance. The present study was undertaken to investigate the bone mineral density (BMD) in women with essential hypertension by means of the dual-energy X-ray absorptiometric (DXA) method. The DXA analysis showed a significant decrease in BMD in female hypertensive subjects compared with normotensive subjects. In addition, the BMD was inversely correlated with systolic blood pressure in women. The 24-h urinary calcium excretion was significantly greater in female hypertensive subjects than in female normotensive subjects. Furthermore, the greater the urinary calcium excretion, the lower the BMD in women. The values of serum total calcium, total magnesium, ionized calcium, and 1, 25(OH)2 vitamin D were not different between hypertensive and normotensive subjects. The results of the present study demonstrated that DXA provided an index of whole calcium balance, and suggest that high blood pressure might be associated with reduced BMD in female hypertension.

Leptin improves membrane fluidity of erythrocytes in humans via a nitric oxide-dependent mechanism—an electron paramagnetic resonance investigation

Abnormalities in physical properties of the cell membranes may underlie the defects that are strongly linked to hypertension, stroke, and other cardiovascular diseases. Recently, there has been an indication that leptin, the product of the human obesity gene, actively participates not only in the metabolic regulations but also in the control of cardiovascular functions. In the present study, to assess the role of leptin in the regulation of membrane properties, the effects of leptin on membrane fluidity of erythrocytes in humans are examined. The membrane fluidity of erythrocytes in healthy volunteers by means of an electron paramagnetic resonance (EPR) and spin-labeling method is determined. In an in vitro study, leptin decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS obtained from EPR spectra of erythrocyte membranes in a dose-dependent manner in healthy volunteers. The finding indicated that leptin increased the membrane fluidity and improved the microviscosity of erythrocytes. The effect of leptin on the membrane fluidity was significantly potentiated by the nitric oxide (NO) donors, L-arginine and S-nitroso-N-acetylpenicillamine (SNAP), and a cyclic guanosine monophosphate (cGMP) analog, 8-bromo-cGMP. In contrast, the change evoked by leptin was significantly attenuated in the presence of the NO synthase inhibitors, N(G)-nitro-L-arginine-methyl-ester (L-NAME) and asymmetric dimethyl-L-arginine (ADMA). The results of the present study showed that leptin increased the membrane fluidity and improved the rigidity of cell membranes to some extent via an NO- and cGMP-dependent mechanism. Furthermore, the data also suggest that leptin might have a crucial role in the regulation of rheological behavior of erythrocytes and microcirculation in humans.

Nitric oxide is a determinant of membrane fluidity of erythrocytes in postmenopausal women: an electron paramagnetic resonance investigation ☆

In the present study, to determine a possible role of nitric oxide (NO) in the regulation of membrane functions, we examined the relationship between plasma NO level and membrane fluidity of erythrocytes in postmenopausal women. We evaluated the membrane fluidity of erythrocytes obtained from hypertensive and normotensive postmenopausal women by means of an electron paramagnetic resonance (EPR) and spin labeling method. The EPR study revealed that the order parameter (S) for 5-nitroxide stearate in erythrocyte membranes was significantly greater in hypertensive postmenopausal women than in normotensive postmenopausal women. The finding indicated that the membrane fluidity of erythrocytes was decreased in hypertensive postmenopausal women compared with normotensive postmenopausal women. The plasma level of the NO metabolites (nitrite and nitrate) while fasting was significantly lower in hypertensive postmenopausal women than in normotensive postmenopausal women. In addition, the order parameter (S) in the EPR spectra of erythrocyte membranes was inversely correlated with the plasma NO metabolite level, which indicated that the lower membrane fluidity of erythrocytes was associated with the lower plasma NO level in postmenopausal women. These results are consistent with the hypothesis that NO may have a crucial role in the regulation of membrane fluidity of erythrocytes in postmenopausal women.

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.

Renin-Angiotensin System and Sympathetic Neurotransmitter Release in the Central Nervous System of Hypertension

Many Studies suggest that changes in sympathetic nerve activity in the central nervous system might have a crucial role in blood pressure control. The present paper discusses evidence in support of the concept that the brain renin-angiotensin system (RAS) might be linked to sympathetic nerve activity in hypertension. The amount of neurotransmitter release from sympathetic nerve endings can be regulated by presynaptic receptors located on nerve terminals. It has been proposed that alterations in sympathetic nervous activity in the central nervous system of hypertension might be partially due to abnormalities in presynaptic modulation of neurotransmitter release. Recent evidence indicates that all components of the RAS have been identified in the brain. It has been proposed that the brain RAS may actively participate in the modulation of neurotransmitter release and influence the central sympathetic outflow to the periphery. This paper summarizes the results of studies to evaluate the possible relationship between the brain RAS and sympathetic neurotransmitter release in the central nervous system of hypertension.

Effects of mild aerobic physical exercise on membrane fluidity of erythrocytes in essential hypertension

1. The present study was undertaken to investigate the effects of aerobic physical exercise on membrane function in mild essential hypertension.

Synergistic role of progesterone and nitric oxide in the regulation of membrane fluidity of erythrocytes in humans: an electron paramagnetic resonance investigation ☆

BACKGROUND It has been shown that progesterone may actively participate in the regulation of blood pressure and other cardiovascular regulations. However, the precise mechanism underlying its effects is unclear. METHODS In the present study, we examined the effects of progesterone on membrane fluidity of erythrocytes in healthy volunteers by means of an electron paramagnetic resonance (EPR) and spin-labeling method. RESULTS In an in vitro study, progesterone significantly decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS obtained from EPR spectra of erythrocyte membranes. The finding indicates that progesterone might increase the membrane fluidity and improve the membrane microviscosity of erythrocytes. The effect of progesterone was significantly potentiated by the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP) and a cyclic guanosine monophosphate (cGMP) analogue, 8-bromo-cGMP. In contrast, the change in the membrane fluidity evoked by progesterone was attenuated in the presence of the NO synthase inhibitors, N(G)-nitro-L-arginine-methyl-ester (L-NAME) and asymmetric dimethyl-L-arginine (ADMA). CONCLUSIONS The results of the present study showed that progesterone increased the membrane fluidity of erythrocytes and ameliorated the rigidity of cell membranes, at least in part, by an NO-dependent mechanism. Furthermore, the data strongly suggest that progesterone might be involved in the regulation of rheological behavior of erythrocytes and have a crucial role in the improvement of microcirculation in humans.

Leukemia inhibitory factor relaxes arteries through endothelium-dependent mechanism

Leukemia inhibitory factor (LIF) is a cytokine, which inhibits angiogenesis and decreases endothelial cell proliferation and migration, suggesting that LIF may modulate vascular tone. In this study, we examined the effects of LIF on the tone of rat arteries. The isometric tension of ring preparations from rat superior mesenteric arteries was continuously measured. LIF relaxed the mesenteric arteries in a dose-dependent manner, when the arterial rings were precontracted with phenylephrine. The relaxation was totally inhibited by mechanical removal of endothelium. N(G)-nitro-L-arginine methyl ester did not affect the relaxation by LIF. Ca(2+)-dependent K channel (KCa) blockers, apamin with charybdotoxin, inhibited the relaxation by LIF. Catalase, an enzyme which scavenges hydrogen peroxide, also inhibited the relaxation by LIF. Endothelium-derived hyperpolarizing factor relaxes smooth muscle cells and the effect is blocked by KCa and catalase. Our results suggest that LIF regulates vascular tone through the effect of this factor.

Associations between High-Sensitivity C-Reactive Protein and Membrane Fluidity of Red Blood Cells in Hypertensive Elderly Men: An Electron Spin Resonance Study

Recent evidence indicates that high-sensitivity C-reactive protein (hs-CRP), an acute phase of an inflammatory marker, might be associated with atherosclerosis, hypertension, and other cardiovascular diseases. The present study was performed to assess the possible link between plasma hs-CRP and membrane fluidity (a reciprocal value of membrane microviscosity) in hypertensive elderly men. We measured the membrane fluidity of red blood cells (RBCs) in hypertensive and normotensive elderly men using an electron spin resonance and spin-labeling method. Membrane fluidity of RBCs was decreased in hypertensive elderly men compared with normotensive elderly men. Plasma hs-CRP levels were significantly higher in hypertensive elderly men than in normotensive elderly men. In contrast, plasma nitric-oxide- (NO-) metabolite levels were lower in hypertensive elderly men than in normotensive elderly men. The reduced membrane fluidity of RBCs was associated with increased plasma hs-CRP and decreased plasma NO-metabolite levels. In a multivariate regression analysis, plasma hs-CRP was an independent determinant of membrane fluidity of RBCs after adjustment for general risk factors. The results suggest that CRP might have a close correlation with the rheologic behavior of RBCs and the microcirculation and would contribute, at least in part, to the circulatory dysfunction and vascular complications in hypertensive elderly men.

Roles of Adiponectin and Oxidative Stress in the Regulation of Membrane Microviscosity of Red Blood Cells in Hypertensive Men—An Electron Spin Resonance Study

This study was undertaken to investigate possible relationships among plasma adiponectin, 8-iso-prostaglandin F2α (8-iso-PG F2α: an index of oxidative stress), and membrane fluidity (a reciprocal value of microviscosity) in hypertensive and normotensive men using an electron spin resonance-method. The order parameter (S) for the spin-label agent (5-nitroxide stearate) in red blood cell (RBC) membranes was higher in hypertensive men than in normotensive men, indicating that membrane fluidity was decreased in hypertension. Plasma adiponectin and NO metabolites levels were lower in hypertensive men than in normotensive men. In contrast, plasma 8-iso-PG F2α levels were increased in hypertensive men compared with normotensive men. Plasma adiponectin concentration was correlated with plasma NO-metabolites, and inversely correlated with plasma 8-iso-PG F2α. The order parameter (S) of RBCs was inversely correlated with plasma adiponectin and plasma NO metabolite levels, and positively correlated with plasma 8-iso-PG F2α, suggesting that the reduced membrane fluidity of RBCs might be associated with hypoadiponectinemia, endothelial dysfunction, and increased oxidative stress. In a multivariate regression analysis, adiponectin and 8-iso-PG F2α were significant determinants of membrane fluidity of RBCs after adjustment for general risk factors. These results suggest that adiponectin and oxidative stress might have a close correlation with rheologic behavior and microcirculation in hypertension.