Hydrogen peroxide activates Na(+)-dependent Ca(2+) influx in coronary endothelial cells

The purpose of the present study was to examine the effect of short duration H(2)O(2) exposure on coronary artery endothelial cell [Ca(2+)](i) regulation. Freshly dispersed cells from porcine coronary artery were exposed to H(2)O(2) (300 micromol/L) for 3 min while monitoring [Ca(2+)](i) using fura-2 microfluorometry. H(2)O(2) increased [Ca(2+)](i) from 0.86 +/- 0.03 to 2.19 +/- 0.41 ratio units at 3 min of H(2)O(2) (P < 0.05). Intracellular Ca(2+) remained elevated 3 min following removal of H(2)O(2), yet H(2)O(2) had no effect on the subsequent [Ca(2+)](i) response to bradykinin (0.1 micromol/L). The H(2)O(2)-induced [Ca(2+)](i) increase was completely abolished either by removal of extracellular Ca(2+) or lowering extracellular Na(+). Cells exposed to the Na(+) ionophore, monensin, showed an increase in [Ca(2+)](i) with a time course similar to that seen with H(2)O(2). Furthermore, H(2)O(2)-induced Ca(2+) influx was not attenuated by either Ni(2+) (300 micromol/L) or econazole (10 micromol/L), excluding Ca(2+) influx via the agonist-sensitive pathway. Thus, in coronary arterial endothelial cells, H(2)O(2) increases Ca(2+) influx in an extracellular Na(+)-dependent manner via an agonist-insensitive pathway.