Differential regulation of L-arginine transport and nitric oxide production by vascular smooth muscle and endothelium.
Since NO production is dependent on the availability of L-arginie, 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 (approximately 70%) and was mediated by both a high- and low-affinity transport system. Treatment of BASMCs with tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta) resulted in a significant increase in L-arginine transport (approximately 20%) and in the induction of NO release. Exposure of BASMCs to interferon gamma (IFN-gamma) or lipopolysaccharide (LPS) also stimulated NO release but did not affect L-arginine transport. In contrast, incubation of BAECs with TNF-alpha or LPS strikingly enhanced L-arginine uptake (2.5-fold), whereas IL-1 beta and IFN-gamma 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.
Durante
W
W
Houston VA Medical Center, TX 77030, USA.
Liao
L
L
Iftikhar
I
I
O'Brien
W E
WE
Schafer
A I
AI
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D012964:Sodium / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D001120:Arginine; D012964:Sodium