| Co-Investigator(Kenkyū-buntansha) |
KURODA Yasuhiro University Hospital, The University of Tokushima, Associate Professor, 医学部・附属病院, 助教授 (80234615)
OSHITA Syuzo School of Medicine, The University of Tokushima, Professor, 医学部, 教授 (60144945)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Research Abstract |
Background: Inhibition of volume-sensitive chloride channels (VSCC) could produce both cardioprotection and cardiotoxicity. Propofol provides cardioprotection against ischemia-reperfusion injury, although cardiotoxicity is also reported. In this study, we investigated the effects of propofol on VSCC in cultured human coronary artery smooth muscle cells using fluorescence measurement. Methods: The chloride-sensitive dye, 6-methoxy-N-ethylquinolinium (MEQ), was loaded into cultured human coronary artery smooth muscle cells. To activate VSCC, hypotonic challenge was performed in the presence of gluconate- for 2 min. The percent reduction in MEQ fluorescence during a following period of 60 sec in the presence of SCN- was measured and used as an index of VSCC activity. Fivenitro-2- (3-phenylpropylamino) benzoic acid (NPPB), a well-characterized chloride channel blocker, and propofol were dissolved in hypotonic gluconate solution to test their effect on VSCC activity. Results: The reduction in fluorescence was inversely related to osmolality, indicating that activation of VSCC is osmolality-dependent. Hypotonic gluconate solution (210 mOsm/kg H2O) reduced fluorescence by 38.4 ± 2.6 %. The reduction in fluorescence due to hypotonic gluconate solution was dose-dependently inhibited by NPPB. Propofol at 0.3, 1, 3, 10, 30 and 100 ug/ml also significantly inhibited the reduction in fluorescence in hypotonic gluconate solution (210 mOsm/kg H2O) to 23.6 ±4.8 %, 19.7±7.4 %, 18.2±3.5 %, 17.6±5.0 %, 15.8±3.1 % and 10.3±3.9 %, respectively. Conclusions: Our results indicate that propofol inhibits VSCC in dose-dependent manner in cultured human coronary artery smooth muscle cells. This may explain in part both cardioprotective and cardiotoxic effects of propofol.
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