Effect of anti-inflammatory drugs on the membrane potential of vascular endothelial cells in vitro.

1 Cells of the aortic endothelium isolated from the guinea-pig and bathed at 37 degrees C with a calcium-free superfusion fluid had membrane potentials of minus 41 plus or minus 7 mV (mean plus or minus s.e mean). 2 Depolarization was produced by addition of potassium (50-200 mM) or certain other monovalent metal cations to the superfusion fluid. Depolarization was rapidly reversed on return to the original superfusate. 3 Several divalent metal cations, notably calcium (16 mM), caused depolarization which was only slowly and incompletely reversed on return to the original calcium-free superfusate. 4 Repolarization after exposure to calcium was accelerated and made more complete by addition of indomethacin (0.25 mM) to the superfusate, 5 The trivalent cations of lanthanum, aluminium or iron (0.1 mM) inhibited the depolarizing effect of calcium (16 mM). 6 Exposure to histamine (100 mug/ml) or heating to 45 degrees C for 1 h caused depolarization in the presence but not in the absence of calcium. Subsequent removal of histamine or cooling again to 37 degrees C in the continued presence of calcium permitted only slow and partial repolarization. However, repolarization was more rapid and complete in the presence of indomethacin (0.25 mM). 7 Heating to 45 degrees C for 5 h in the presence of calcium caused progressive and almost complete depolarization. Lanthanum, cinchocaine, indomethacin, flufenamic, meclofenamic and salicylic acids, phenylbutazone and aminopyrine each reduced the depolarization, but hydrocortisone, chloroquine, benzindamine, isoprenaline and aminophylline did not.