ISRADIPINE AFFECTS HISTAMINE-INDUCED CYTOSOLIC CA2-CELLS( MOVEMENTS IN HUMAN ENDOTHELIAL)

Although endothelial actions of dihydropyridines remain controversial, isradipine has been observed to exert anti-atherosclerotic actions in which endothelium could be involved. This study was designed to inves tigate the direct effects of isradipine on cytosolic Ca2+ concentratio n in cultured human umbilical vein endothelial cells. Isradipine (from 10 nM to 1 mu M) had no effect on unstimulated cells but dose-depende ntly decreased both the transient [Ca2+](i) peak and the sustained inc rease induced by histamine. Its maximal effects were reached at 0.1 mu M. In the absence of Ca2+ influx or in depolarized cells, 1 mu M isra dipine still significantly decreased the transient [Ca2+](i) peak (by 23 +/- 8% and 42 +/- 11%). Ca2+ influx induced by re-establishment of transmembrane Ca2+ gradient was also inhibited by isradipine, as was t hat induced by 1 mu M thapsigargin. These results demonstrate that isr adipine is able to reduce both Ca2+ release from internal stores and t he consequent Ca2+ entry in stimulated human endothelial cells.