Effect of propofol on hypotonic swelling-induced membrane depolarization in human coronary artery smooth muscle cells.
BACKGROUND
Stretch (mechanical stress)-induced membrane depolarization of smooth muscle may contribute to basal vascular tone and myogenic control. Propofol induces vasodilation and inhibits myogenic control. Hypotonic swelling was used as a model of mechanical stress. The authors investigated the effects of propofol and 5-nitro-2-(3-phenylpropylamino)benzoic acid, a chloride channel and nonselective cation channel blocker, on hypotonicity-induced membrane depolarization in cultured human coronary artery smooth muscle cells.


METHODS
A voltage-sensitive fluorescent dye, bis-(1,3-diethylthiobarbiturate)trimethine oxonol, was used to assess relative changes in membrane potential semiquantitatively. The cells were continuously perfused with Earle's balanced salt solution containing 200 nM bis-(1,3-diethylthiobarbiturate)trimethine oxonol and exposed sequentially to isotonic and hypotonic medium. In a second series of experiments, the cells were exposed to hypotonic media in the presence and absence of 5-nitro-2-(3-phenylpropylamino)benzoic acid or propofol.


RESULTS
The relative fluorescence values at 10, 20, and 30% hypotonicity were 147 +/- 29, 214 +/- 74, and 335 +/- 102% of baseline, respectively. The changes were all significantly different from the isotonic time control group. In the presence of 200 microM 5-nitro-2-(3-phenylpropylamino)benzoic acid or 0.1, 1, 10, or 100 microg/ml propofol, the relative fluorescence values at 30% hypotonicity were 87 +/- 17, 194 +/- 27, 160 +/- 18, 130 +/- 18, and 84 +/- 15%, respectively. These changes were significantly less than the 30% for the hypotonic control (246 +/- 23%).


CONCLUSIONS
These results suggest that volume-sensitive chloride channels and nonselective cation channels may participate in hypotonicity-induced membrane depolarization and that propofol inhibits hypotonicity-induced membrane depolarization in coronary artery smooth muscle.
Masuda
Takako
T
Department of Anesthesiology, Tokushima University School of Medicine, Japan.
Tomiyama
Yoshinobu
Y
Kitahata
Hiroshi
H
Kuroda
Yasuhiro
Y
Oshita
Shuzo
S
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D002138:Calibration; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D003331:Coronary Vessels / Q000166:cytology* / Q000187:drug effects; D005456:Fluorescent Dyes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007038:Hypotonic Solutions; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D009579:Nitrobenzoates / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D018118:Chloride Channels; D005456:Fluorescent Dyes; D007038:Hypotonic Solutions; D007473:Ion Channels; D009579:Nitrobenzoates; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D012964:Sodium; D011188:Potassium; D015742:Propofol