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Am J Physiol Renal Physiol 283: F578-F582, 2002. First published March 19, 2002; doi:10.1152/ajprenal.00355.2001
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Vol. 283, Issue 3, F578-F582, September 2002

Urea transporters are distributed in endothelial cells and mediate inhibition of L-arginine transport

Laszlo Wagner1,2, Janet D. Klein3, Jeff M. Sands3, and Chris Baylis1

1 Department of Physiology, West Virginia University, Morgantown, West Virginia 26506-9229; 2 Nephrological Center, Second Department of Medicine, University Medical School of Pecs, H-7624 Pecs, Hungary; and 3 Renal Division, Emory University, Atlanta, Georgia 30322

Our laboratory previously reported that uremic levels of urea inhibit L-arginine (L-Arg) transport into endothelial cells. The present study further investigated this effect. We measured L-Arg transport in cultured bovine aortic endothelial cells with normal or high urea (25 mM). The urea transport inhibitor phloretin abolished the inhibitory effect of urea on L-Arg transport, suggesting a role for urea transporters (UTs). We screened bovine aortic endothelial cells and several other endothelial cell types for the presence of UTs by using Western blot analysis. UT-B was present in all endothelial cells, irrespective of species or location of derivation, whereas UT-A distribution was variable and sparse. UT-B was also abundant in rat aorta, mesenteric blood vessels, and spinotrapezius muscle, whereas UT-A distribution was, again, variable and sparse. Chronic elevation of urea had variable, inconsistent effects on UT abundance. This study showed that urea must enter endothelial cells, probably by UT-B, to inhibit L-Arg transport. In view of the wide distribution of UT-B in rat vasculature, elevated blood urea nitrogen may lead to endothelial L-Arg deficiency in vivo.

uremia; nitric oxide; phloretin; blood vessels


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