Intracellular and extracellular Ca2+ regulate histamine-induced release of nitric oxide in vascular endothelial cells as shown with sensitive and selective nitric oxide electrodes.

The effects of various agents that alter the intracellular Ca2+ concentration and the extracellular Ca2+ concentration on histamine-induced release of nitric oxides (NO) from porcine aortic endothelial cells were studied using NO electrodes. The NO release induced by application of histamine (200 microM) in Ca(2+)-free solution was similar to that in solution with a normal Ca2+ concentration on its first application, but reduced on its second application. NO release was also suppressed by 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA), which lowers the intracellular Ca2+ concentration, and was completely inhibited by Co2+, but it was not affected by verapamil, a voltage-dependent Ca2+ channel blocker. These results suggest that Ca2+ release from intracellular stores might play an important role in NO production, that influx of extracellular Ca2+ is required to refill the stores, and that this Ca2+ influx is not through voltage-dependent Ca2+ channels.