| Project/Area Number |
04670510
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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 | Hokkaido University |
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Principal Investigator |
SAKURADA Keisuke (1993) Hokkaido University School of Medicine Lecturer, 医学部, 講師 (80002161)
松野 一彦 (1992) 北海道大学, 医学部, 助教授 (70102332)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUNO Kazuhiko Hokkaido University School of Medicine Associate Professor, 医学部, 助教授 (70102332)
桜田 恵右 北海道大学, 医学部, 講師 (80002161)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Sodium / Calcium / Platelet / Hypertension / SBFI / マグネシウム |
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| Research Abstract |
We established the method for measurement of cytosolic free sodium ion concentration ([Na^+]i) in platelets using new fluorescent Na^+-indicator, sodium-binding benzofuran isophthalate (SBFI). The problems of this measurement were 1) the method for loading of SBFI into cytoplasm, 2) impairment of platelet function by loading of SBFI, 3) the method for calibration, 4) low value of Kd for SBFI.This method leaves much to be desired.
In this method, [Na^+]i was 33.6 (〕SY.+-.〔) 12.6 mM in resting platelets of healthy volunteers, and elevated to over 80 mM by the stimulation with thrombin. Increased [Na^+]i was consider to depend mainly on influx from extracellular space into cytoplasm, because the removal of extracellular Na^+ inhibited increase in [Na^+]i.
Na^+/H^+ exchange and common pathway as Ca^<2+> influx were implicated in Na^+ influx. Inhibition of Na^+/K^+- ATPase by ouabain enhanced thrombin-induced increase in [Ca^<2+>]i and platelet aggregation.
[Na^+]i was 40.2 (〕SY.+-.〔) 9.1 mM in resting platelets of 15 untreated patients with essential hypertension (EHT), and this was significantly higher than in healthy controls (34.2 (〕SY.+-.〔) 6.3mM). [Ca^<2+>]i was significantly higher in EHT patients than in controls (92.6 (〕SY.+-.〔) 16.9 nM vs 76.9 (〕SY.+-.〔) 12.3 nM). There was no difference in [Na^+]i in thrombin-stimulated platelets of EHT and controls, but [Ca^<2+>]i in thrombin-stimulated platelets of EHT was significantly higher than in controls. Thrombin-induced platelet aggregation was higher in EHT than in controls.
There was a close correlation between platelet aggregation and [Ca^<2+>]i, but not [Na^+]i.
[Na^+]i was elevated in platelets of patients with EHT.We speculated that increased intracellular Na^+ inhibited Na^+/Ca^<2+> exchange, leading to increased [Ca^<2+>]i and enhanced platelet aggregation.
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