68 ENDOTHELIAL CELLS (EC) TOLERATE PROLONGED HYPOXIA AND GLUCOSE DEPRIVATION

Abstract

ECs play a key role in organ damage after ischemia-reperfusion and oxygen toxicity. In vitro models have been described in which short-term exposure of ECs to hypoxia followed by hyperoxia causes cell damage. We cultured human ECs from umbilical veins, prelabeled them with 14C-adenine, and followed nucleotide catabolism as a sensitive indicator of cell damage during exposure to normoxia (N), 95% N2 + 5% CO2 (HYPO), or 95% O2 + 5% CO2 (HYPER), with either 0 or 5.5 mM glucose (G) in the medium. Up to 6h, adenine nucleotide turnover and hypoxanthine accumulation in the medium were similar under all incubation conditions. After 16h, cellular nucleotide levels, in comparison with N+G (=100+-9 %), Were:N-G 140+-17 %, HYPO+G 37+-9 %, HYPO-G 58+-2%, HYPER+G 16+-7 %, and HYPER-G 114+-35 %. When 16h of HYPO was followed by 8h of HYPER, depletion was total and cell death ensued in the presence and absence of G. We conclude that ECs tolerate both HYPO and G deprivation for several hours, and surprisingly they are more sensitive to both HYPO and HYPER in the presence than in the absence of G.