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.
Schmidt
H H
HH
Institut für Pharmakologie, Freie Universität Berlin, Federal Republic of Germany.
Zernikow
B
B
Baeblich
S
S
Böhme
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002172:Canavanine / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism*
D009566:Nitrates; D009573:Nitrites; D009589:Nitrogen Oxides; D009569:Nitric Oxide; D000001:Calcimycin; D002172:Canavanine; D000255:Adenosine Triphosphate; D001120:Arginine; D000109:Acetylcholine; D001920:Bradykinin