Differential Regulation of l -Arginine Transport and Nitric Oxide Production by Vascular Smooth Muscle and Endothelium

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Abstract
Since NO production is dependent on the availability of l -arginine, we examined whether l -arginine transport and NO synthesis are coregulated by vascular smooth muscle cells and endothelial cells cultured from the same vessel wall source. l -Arginine transport by both bovine aortic smooth muscle cells (BASMCs) and endothelial cells (BAECs) was primarily Na + independent (≈70%) and was mediated by both a high- and low-affinity transport system. Treatment of BASMCs with tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β) resulted in a significant increase in l -arginine transport (≈20%) and in the induction of NO release. Exposure of BASMCs to interferon gamma (IFN-γ) or lipopolysaccharide (LPS) also stimulated NO release but did not affect l -arginine transport. In contrast, incubation of BAECs with TNF-α or LPS strikingly enhanced l -arginine uptake (2.5-fold), whereas IL-1β and IFN-γ had no effect. Treatment of BAECs with any of the inflammatory mediators did not stimulate NO production. These results demonstrate that l -arginine uptake and NO synthesis by these cells are differentially regulated. In BASMCs, the coinduction of l -arginine transport and NO formation may function to provide increased levels of substrate to the cell during activation of the NO synthase enzyme. In contrast, the selective stimulation of l -arginine uptake in BAECs indicates that l -arginine transport is dissociated from NO generation in these cells.

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