Hypoxia inhibits l-arginine uptake by pulmonary artery endothelial
cells.
Block, Edward R., Humberto Herrera, and Margaret Couch.
Research Service of the Veterans Affairs Medical Center and the
Department of Medicine, University of Florida, Gainesville, FL
USA
APStracts 2:0095L, 1995.
Under physiologic conditions, L-arginine transport by porcine
pulmonary artery endothelial cells (PAEC) is mediated by System y+, a
sodium-independent transport system that accounts for 60 +/- 5% of L
-arginine transport, and System Bo,+, a sodium-dependent agency that
accounts for 40 +/- 5% of transport. Because NO production is
dependent upon intracellular L-arginine content and intracellular L
-arginine content depends upon transport of extracellular L-arginine,
we examined the effect of hypoxia on L-arginine transport and
intracellular L-arginine content in PAEC. Exposure of third-to
-seventh passage PAEC in monolayer culture to 0% O2 for 4 h decreased
L-arginine transport via System y+ from 120 +/- 10 to 81 +/- 23
pmol/mg protein/30 sec (P < 0.001) whereas 20-h exposures
decreased transport from 122 +/- 17 to 84 +/- 18 (P < 0.001) in
System y+ and from 104 +/- 19 to 90 +/- 26 (P < 0.05) in System
Bo,+. Exposure to 5% O2 for 3 to 5 weeks decreased L-arginine
transport via System y+ from 128 +/- 15 to 73 +/- 13 (P < 0.001)
and via System Bo,+ from 105 +/- 25 to 65 +/- 13 pmol/mg protein/30
sec (P < 0.001). Kinetic studies revealed that hypoxia decreased
the Vmax but not the Km for both System y+ and System Bo,+, and the
decreases in transport were not reversible following return to
normoxia for up to 24 h. Long-term exposure, i.e. 3 to 5 weeks, to 5%
O2 also resulted in decreases in intracellular L-arginine content
(0.75 +/- 0.10 vs 0.49 +/- 0.09 nmol/106 cells, P < 0.05) which
did not reverse following return to normoxia for 24 h. Reductions in
L-arginine uptake may impair NO production by hypoxic pulmonary
endothelium by decreasing the availability of intracellular L
-arginine.
Received 27 January 1995; accepted in final form 31 May 1995.
APS Manuscript Number L26-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.