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Am. J. Respir. Cell Mol. Biol., Volume 26, Number 3, March, 2002 348-355

L-Arginine Uptake and Metabolism following in vivo Silica Exposure in Rat Lungs

Leif D. Nelin, Gary S. Krenz, Louis G. Chicoine, Christopher A. Dawson, and Ralph M. Schapira

Vascular Physiology Group and Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New Mexico; Departments of Pediatrics, Physiology, and Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; and Department of Mathematics, Statistics, and Computer Science, Marquette University, Milwaukee, Wisconsin; and Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin

Pulmonary inflammation increases nitric oxide (NO) production via inducible nitric oxide synthase (iNOS). This study was performed to determine some of the factors that affect the availability of the NOS substrate, L-arginine (L-arg), in the intact lung subjected to silica-induced inflammation. Nitrate production, as an index of NO production, was significantly greater in silica-exposed lungs (53.5 ± 12.1 nmol/90 min) compared with controls (22.5 ± 5.1 nmol/90 min, P < 0.05). This was accompanied by greater (P < 0.0001) 90-min [3H]L-arg uptake (62 ± 3% control, 82 ± 1% silica), a significantly (P < 0.005) increased permeability-surface area product for L-arg (0.28 ± 0.05 ml/min control, 0.63 ± 0.07 ml/min silica), and a significantly (P < 0.001) increased urea production (1.16 ± 0.08 µmol/90 min control, 1.77 ± 0.06 µmol/90 min silica). There was no difference in eNOS protein between groups and eNOS mRNA was not detectable in either group, whereas silica exposure resulted in the appearance of both iNOS protein and mRNA. Silica exposure increased CAT-1 and CAT-2 mRNA ~ 8-fold compared with controls. We conclude that the increase in NO production in silica-exposed lungs was associated with increased L-arg uptake from the vasculature, presumably resulting from increased CAT-1 and CAT-2, and by increased L-arg metabolism via arginase.

Abbreviations: arginase, AR; inducible nitric oxide synthase, iNOS; L-arginine, L-arg; nitric oxide, NO; nitrite/nitrate, NOX; thin-layer chromatography, TLC.




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