Basal and stimulated formation and release of L-arginine-derived nitrogen oxides from cultured endothelial cells.

Endothelium-derived nitrogen oxides, i.e., nitrogen oxide and/or nitrogen oxide-containing compounds, formed from L-arginine account, at least in part, for the biological activity of endothelium-derived relaxing factor(s). We have developed a rapid and sensitive assay to determine the basal and stimulated release of defined breakdown products of endothelium-derived nitrogen oxides, i.e., nitrite and nitrate. Formation and/or release of these nitrogen oxides was time- and concentration-dependently stimulated by various endothelium-dependent vasodilators and was decreased by NG-methyl-L-arginine and L-canavanine, compounds that most likely inhibit the endothelial enzymatic conversion of L-arginine into nitrogen oxides. In addition to nitrogen oxide, hydroxylamine was shown to have pharmacological and physico-chemical properties similar to endothelium-derived relaxing factor(s). Moreover, hydroxylamine release was detected in stimulated bovine aortic endothelial cells. We suggest that hydroxylamine represents one endothelium-derived nitrogen oxide within the group of biologically active nitrogen oxides.