Cellular disposition of transported polyamines in hypoxic rat lung and pulmonary arteries

The polyamines putrescine, spermidine (SPD), and spermine are a family of l ow-molecular-weight organic cations essential for cell growth and different iation and other aspects of signal transduction. Hypoxic pulmonary vascular remodeling is accompanied by depressed lung polyamine synthesis and marked ly augmented polyamine uptake. Cell types in which hypoxia induces polyamin e transport in intact lung have not been delineated. Accordingly, rat lung and rat main pulmonary arterial explants were incubated with [C-14]SPD;, ei ther normoxic (21% O-2) or hypoxic (2% Oz) environments for 24 h. Autoradio graphic evaluation confirmed previous studies showing that, in normoxia, al veolar epithelial cells are dominant sites of polyamine uptake. In contrast , hypoxia was accompanied by prominent localization of [14C] SPD i, conduit , muscularized, and partially muscularized pulmonary arteries, which was no t evident in normoxic lung tissue. Hypoxic main pulmonary arterial explants also exhibited substantial increases in [14C]SPD uptake relative to contro l explants, and autoradiography revealed that enhanced uptake was most evid ent in the medial layer. Main pulmonary arterial explants denuded of endoth elium failed to increase polyamine transport in hypoxia. Conversely, medium conditioned by endothelial cells cultured in hypoxic, but not in normoxic, environments enabled hypoxic transport induction in denuded arterial expla nts. These findings in arterial explants were recapitulated in rat cultured main pulmonary artery cells, including the enhancing effect of a soluble e ndothelium-derived factor(s) on hypoxic induction of [C-14]SPD uptake in sm ooth muscle cells. Viewed collectively, these results show in intact lung t issue that hypoxia enhances polyamine transport in pulmonary artery smooth muscle by a mechanism requiring elaboration of an unknown factor(s) from en dothelial cells.