Lipopolysaccharide and Tumor Necrosis Factor Stimulate Lung Microvascular Arginine Uptake, a Response Attenuated by

crosis factor-α, (TNF), and glucocorticoids can modulate endot-helial nitric oxide (NO) production. L-Arginine is the exclusive precursor for NO biosynthesis, suggesting that NO generation and arginine transport are intimately linked. Methods: To further study this relationship, we examined the effects of LPS, TNF, and dexamethasone (DEX) on arginine uptake by rat lung mi-crovascular endothelial cells. The transport of radiolabeled argi-nine was assayed in confluent cells grown in 24-well plates. Re-sults: The bulk (>90%) of arginine transport was mediated by the Na+-independent carriers System y+ and System b0,+. Arginine transport was stimulated independently by LPS and TNF, a re-sponse first observed at 10 hours. Together, both agents exerted an additive effect on carrier-mediated uptake. The LPS- and TNF-induced increase in arginine transport activity was blocked by cycloheximide and actinomycin D, indicating the requiremen