ENDOTHELIAL-CELL TOLERANCE TO HYPOXIA - POTENTIAL ROLE OF PURINE NUCLEOTIDE PHOSPHATES

The ability of cells to tolerate hypoxia is critical to their survival , but varies greatly among different cell types. Despite alterations i n many cellular responses during hypoxic exposure, pulmonary arterial endothelial cells (PAEC) retain their viability and cellular integrity . Under similar experimental conditions, other cell types, exemplified by renal tubular epithelial cells, are extremely hypoxia sensitive an d are rapidly and irreversibly damaged. To investigate potential mecha nisms by which PAEC maintain cellular and functional integrity under t hese conditions, we compared the turnover of adenine and guanine nucle otides in hypoxia tolerant PAEC and in hypoxia-sensitive renal tubular endothelial cells under various hypoxic conditions. Under several dif ferent hypoxic conditions, hypoxia-tolerant PAEC maintained or actuall y increased ATP levels and the percentage of these nucleotides found i n the high energy phosphates, ATP and GTP. In contrast, in hypoxia-sen sitive renal tubular endothelial cells, the same high energy phosphate s were rapidly depleted. Yet, in both cell types, there were minor alt erations in the uptake of the precusor nucleotide and its incorporatio n into the appropriate purine nucleotide phosphates and marked decreas es in ATPase and GTPase activity. This maintenance of high energy phos phates in hypoxic PAEC suggests that there exists tight regulation of ATP and GTP turnover in these cells and that preservation of these nuc leotides may contribute to the tolerance of PAEC to acute and chronic hypoxia.