Cytotoxicity-Associated Effects of Reactive Oxygen Species on Endothelin-1 Secretion by Pulmonary Endothelial Cells

• Published in: Free radical biology & medicine Vol. 24; no. 9; pp. 1437 - 1445
• Main Authors: Love, Graham P, Keenan, Alan K
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.1998
• Subjects: Animals; Cattle; Cell Survival - drug effects; Cells, Cultured; Cytotoxicity; Endothelial cells; Endothelin-1 - metabolism; Endothelin-1 secretion; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Free radicals; Hydrogen peroxide; Hypoxanthine–xanthine oxidase; Lung - blood supply; Lung - cytology; Lung - drug effects; Pulmonary vasculature; Reactive Oxygen Species - physiology; Hydrogen peroxide; Free radicals; Pulmonary vasculature; Endothelin-1 secretion; Hypoxanthine–xanthine oxidase; Cytotoxicity; Endothelial cells
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(98)00011-2

In this study bovine pulmonary artery endothelial cells (BPAEC) were used as a model system to investigate the effects of the hypoxanthine–xanthine oxidase (HXXO) oxygen radical donor system on ET-1 secretion into pulmonary vasculature. Incubation of BPAEC with HXXO for 4 h caused a significant reduction in ET-1 secretion, which was significantly offset by allopurinol or catalase, but not by Cu/Zn superoxide dismutase (SOD). ET-1 secretion was also reduced by H 2O 2, and this effect was again significantly offset by catalase. XO alone also reduced ET-1 secretion, but to a significantly lesser degree than did HXXO, and this effect was not offset by allopurinol, catalase, or SOD. None of the oxidant treatments were associated with a loss of immunoreactive ET-1 from endothelial cell medium containing synthetic peptide. The HXXO- and H 2O 2-mediated reductions in ET-1 secretion were accompanied by evidence of reduced cell viability. This loss of viability was absent when cells were treated with HXXO + catalase, allopurinol, or mercaptopropionyl glycine, but not when SOD was present. We conclude that under conditions of oxidative stress, the pulmonary vascular endothelium responds by secreting less ET-1. This may be relevant to its vasodilator functions in the pulmonary vasculature, which would therefore be compromised when the endothelium is exposed to oxidant stress.