Isradipine affects histamine-induced cytosolic Ca2+ movements in human endothelial cells

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 investigate the direct effects of isradipine on cytosolic Ca2+ concentration in cultured human umbilical vein endothelial cells. Isradipine (from 10 nM to 1 microM) had no effect on unstimulated cells but dose-dependently decreased both the transient [Ca2+]i peak and the sustained increase induced by histamine. Its maximal effects were reached at 0.1 microM. In the absence of Ca2+ influx or in depolarized cells, 1 microM isradipine 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 that induced by 1 microM thapsigargin. These results demonstrate that isradipine is able to reduce both Ca2+ release from internal stores and the consequent Ca2+ entry in stimulated human endothelial cells.