Transition metals and nitric oxide production in human endothelial cells.

The bioavailability of endothelial nitric oxide (NO) is regulated by transi tion metals but their mechanisms of action on NO synthesis and degradation are not clearly understood. Using differential pulse amperometry and NO mic roelectrodes, local NO concentration was measured at the surface of culture d human umbilical vein endothelial cells (HUVECs) stimulated by histamine o r thrombin in the presence of transition metal chelators. The agonist-activ ated NO release required both extracellular Ca2+ and transition metals. In the presence of 1 mM external Ca2+, a low concentration of EGTA (5 muM) inh ibited by 40 % the NO release from stimulated HUVECs. In the presence of ex tracellular L-arginine, the inhibitory effect of EGTA was even more marked and, in its absence, it was suppressed by adding exogenous superoxide dismu tase. The decrease in NO release induced by the copper chelators, cuprizone and DETC, suggests that extracellular traces of Cu2+ could regulate NO ava ilability. (C) 2001 Academie des sciences / Editions scientifiques et medic ales Elsevier SAS.