EFFECT OF ANTI‐INFLAMMATORY DRUGS ON THE MEMBRANE POTENTIAL OF VASCULAR ENDOTHELIAL CELLS in vitro

Abstract

1Cells of the aortic endothelium isolated from the guinea-pig and bathed at 370 C with a calcium-free superfusion fluid had membrane potentials of -41 ± 7 mV (mean ± s.e. mean). 2 Depolarization was produced by addition of potassium (50-200 mM) 6 Exposure to histamine (100 jig/ml) or heating to 450 C for 1 h caused depolarization in the presence but not in the absence of calcium. Subsequent removal of histamine or cooling again to 370 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 450 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.

INTERACTION OF MONO‐ AND DIVALENT METALLIC CATIONS AND OF INDOMETHACIN ON THE MEMBRANE POTENTIAL OF VASCULAR ENDOTHELIAL CELLS in vitro

“…(Northover, 1975b), it was of interest to establish whether indomethacin would also reduce the depolarizing effect of these other metallic cations. Indomethacin (0.05 and 0.25 mM) failed to alter significantly the depolarizing effect of added potassium or cuprous ions but reduced the influence of exposure for 1 h to added cupric or ferrous ions (Figure 3).…”

“…Membrane potentials of endothelial cells from the thoracic aorta of guinea-pigs were recorded as described previously in detail (Northover, 1975b). The isolated aorta was cut longitudinally and opened out into a sheet which was then tied to the bottom of a superfusion trough.…”

“…An earlier study revealed that vascular endothelial cells possess a resting membrane potential which may be measured in vitro during exposure of the vessel wall to bathing fluids of known composition (Northover, 1975b). Heating the vessel wall to 450 C, or exposing it to histamine, depolarized the endothelial cells if the bathing fluid contained calcium ions but had no effect in the absence of calcium.…”

Histamine‐induced inward currents in cultured endothelial cells from human umbilical vein

“…Alternatively, it may be that the embryonic nature of the umbilical vein underlies differences in cellular behaviour compared to adult tissue or that differences exist between endothelial cells of arterial and venous origin. It has been suggested (Northover, 1975a) that external Ca-dependent, histamine-induced depolarization of endothelial cells is associated with morphological and histochemical changes of the endothelium (Northover, 1975b) seen in intact guinea-pig aorta. The inward current evoked by histamine in human endothelial cells (present work) may generate this depolarization.…”

“…Calcium influx (D'Amore & Shepro, 1977) and intracellular calcium concentration were increased in the presence of histamine (Rotrosen & Gallin, 1986;Hamilton & Sims, 1987). Depolarization of endothelial cells was reported by Northover (1975a; following application of histamine. However, no relationship between rises in internal calcium and changes in endothelial cell membrane permeability has been established.…”