CYTOTOXICITY-ASSOCIATED EFFECTS OF REACTIVE OXYGEN SPECIES ON ENDOTHELIN-1 SECRETION BY PULMONARY ENDOTHELIAL-CELLS

In this study bovine pulmonary artery endothelial cells (BPAEC) were u sed as a model system to investigate the effects of the hypoxanthine-x anthine oxidase (HXXO) oxygen radical donor system on ET-1 secretion i nto pulmonary vasculature. Incubation of BPAEC with HXXO for 4 h cause d a significant reduction in ET-1 secretion, which was significantly o ffset by allopurinol or catalase, but not by Cu/Zn superoxide dismutas e (SOD). ET-1 secretion was also reduced by H2O2, and this effect was again significantly offset by catalase. XO alone also reduced ET-1 sec retion, but to a significantly lesser degree than did HXXO, and this e ffect was not offset by allopurinol, catalase, or SOD. None of the oxi dant treatments were associated with a loss of immunoreactive ET-1 fro m endothelial cell medium containing synthetic peptide. The HXXO- and H2O2-mediated reductions in ET-1 secretion were accompanied by evidenc e of reduced cell viability. This loss of viability was absent when ce lls were treated with HXXO + catalase, allopurinol, or mercaptopropion yl glycine, but not when SOD was present. We conclude that under condi tions of oxidative stress, the pulmonary vascular endothelium responds by secreting less ET-1. This may be relevant to its vasodilator funct ions in the pulmonary vasculature, which would therefore be compromise d when the endothelium is exposed to oxidant stress. (C) 1998 Elsevier Science Inc.