Relation between reduced alveolar PO2 and collagen biosynthesis in the perfused rat lung

Collagen biosynthesis was studied in a perfused rat lung system by measuring the extent of [14C]proline incorporation into TCA-insoluble [14C]hydroxyproline-containing protein over a 2 hr perfusion period. It was found that [14C]hydroxyproline formation was linear over the 2 hr period after an initial lag period of 20 to 30 min. [14C]Hydroxyproline constituted between 5% and 6% of the total [14C]proline incorporation, indicating that about 10% of the proline incorporated went into collagen. In the presence of phosphate buffers, collagen biosynthesis was markedly reduced, although total proline incorporation was unaffected. When lungs were ventilated at progressively lower Po2's, no significant effects were observed until the Po2's were below 12 mm Hg, at which point both [14C]hydroxyproline formation and the percentage of [14C]hydroxyproline declined. The PO2 at which hydroxylation was decreased by 50% was approximately 5 mm Hg. When lungs were ventilated with a 90% carbon monoxide, 5% oxygen, 5% carbon dioxide mixture (PO2, 36 mm Hg), protein synthesis was inhibited but the proline hydroxylation system was unaffected. (J Lab Clin Med 99:441, 1982.)