1997 Fiscal Year Final Research Report Summary
Ca^<2+>-Metabolism and Hypertension
| Project/Area Number |
08670819
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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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, 医学部, 講師 (90217315)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIO Ichiro Wakayama Medical College, Division of Cardiology, Department of Medicine, Profes (40089165)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Hypertension / Protein kinase C / Neurotransmitter release / Membrane Fluidity / Calcium / Sodium / Insulin / Electron paramagnetic resonance |
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| Research Abstract |
The purpose of the present study was to investgate the abnormalities in the Ca^<2+>-and Na^+-metabolism in hypertension. Neuropeptide Y (NPY) significantly inhibited the stimulation-evoked norepinephrine (NE) release in rat medulla oblongata and hypothalamus. Pretreatment of pertussis toxin (a potent inhibitor of the Gi-proteins) attenuated the suppressive effects of NPY on NE release. When the sodium concentration of the perfusion medium was increased, the inhibitory effect of NPY on NE release was significantly reduced. The finding suggests that sodium ions might actively participate in regulating the NPY-mediated functions in the central nervous system. In addition, we examined the effects of Ca^<2+> channel blocker diltiazem and protein kinase C (PKC) inhibitor on central acetycholine (ACh) release in hypertension. Diltiazem inhibited the stimulation-evoked [^3H] ACh release in rat striatum in a dose-dependent manner.
The inhibitory effect was significantly more pronounced in the st
… More
riatum of SHR than in the striatum of WKY rats. The PKC inhibitor H-7 also reduced the stimulation-evoked [^3H]ACh release to a greater extent in SHR than WKY rats. The results show the enhanced Ca^<2+>-PKC system in the regulation of neurotransmitter release in hypertension.
In the next series of the experiments, we studied the changes in membrane fluidity of erythrocytes in patients with essential hypertension (EH) by means of an electron paramagnetic resonance (EPR) method. The erythrosyte membrane fluidity was significantly lower in patients with EH than in normotensive subjects. The Ca^<2+>-loading to erythrocytes decreased the membrane fluidity. The Ca^<2+>-induced change in the fluidity was correlated with age in EH.
Ouabain, the Na^+, K^+-ATPase inhibitor, also reduced the membrane fluidity to a greater extentin EH than in the normotensive controls. On the other hand, insulin decreased the membrane fliuidity of erythrocytes. The effect of insulin was potentiated by Ca^<2+>, and, by contrast, was antagonized by the Ca^<2+>channel blocker diltiazem. From these results, we conclude that abnormalities in the Ca^<2+>-metabolism might actively participate in the pathogenesis of hypertension. Less
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