1994 Fiscal Year Final Research Report Summary
Membrane Functions and Hypertension
| Project/Area Number |
05670631
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Wakayama Medical College |
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Principal Investigator |
TSUDA Kazushi Wakayama Medical College, Division of Cardiology, Department of Medicine, Assistant Professor, 循環器内科, 講師 (90217315)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIO Ichiro Wakayama Medical College, Division of Cardiology, Department of Medicine, Profes, 循環器内科, 教授 (40089165)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Hypertension / Membrane function / Signal transduction / Neurotransmitter release / Excitatory amino acid / Peptide hormone / Membrane fluidity / Electron paramagnetic resonance |
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| Research Abstract |
In the first series of experiments, we describe the results of studies regarding the effects of excitatory amino acids and peptide hormones on neurotransmitter release in the central nervous system of hypertension. The excitatory aino acid, l-glutamate (L-Glu), significantly increased the release of norepinephrine (NE) and acetylcholine (ACh) in rat central nervous system. The effect of L-Glu was potentiated by glycine, and, by contrast, was antagonized by Mg^<2+> and MK-801. The finding suggests that L-Glu might increase the release of NE and ACh, partially mediated by N-methyl-D-aspartate receptors in the central nervous system. On the other hand, neuropeptide Y (NPY) inhibited the stimulation-evoked NE release in rat striatum. A part of the mechanisms might be explained by interactions with presynaptic D2-receptors and the pertussis toxin-sensitive Gi-proteins. Bradykinin increased the stimulation-evoked NE release from rat hypothalamus. The bradykinin-effect might be partially due
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to the facilitation of Ca^<2+> influx through the dihydropyridine-sensitive Ca^<2+> channels in the brain. In spontaneously hypertensive rats (SHR), the effects of L-Glu, NPY and bradykinin were altered compared with age-matched Wistar-Kyoto rats. These results suggests that the excitatory amino acids and peptide hormones might be involved in the regulation of neural activities in hypertension.
In the second series of experiments, we examined changes in membrane fluidity of erythrocytes in patients with essential hypertension by means of an electron paramagnetic resonance (EPR) method. The membrane fluidity of erythrocytes was significantly lower in patients with essential hypertension than in the normotensive controls. The decrease in the fluidity was pronounced in the subjects with a family history of hypertension. Insulin significantly decreased the membrane fluidity of erythrocytes. The insulin-effect was potentiated by Ca^<2+>. From these results, we have drawn the conclusion that abnormalities in membrane functions and their related signal transduction systems might actively participate in the pathogenesis of hypertension. Less
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