Title

L-Arginine uptake and metabolism following in vivo silica exposure in rat lungs

Document Type

Article

Language

eng

Format of Original

8 p.

Publication Date

3-2002

Publisher

American Thoracic Society

Source Publication

American Journal of Respiratory Cell and Molecular Biology

Source ISSN

1044-1549

Abstract

Pulmonary inflammation increases nitric oxide (NO) production via inducible nitric oxide synthase (iNOS). This study was performedto determine some of the factors that affect the availabilityof the NOS substrate, L-arginine (L-arg), in the intact lung subjectedto silica-induced inflammation. Nitrate production, as an indexof NO production, was significantly greater in silica-exposedlungs (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 asignificantly (P < 0.001) increased urea production (1.16 ± 0.08µmol/90 min control, 1.77 ± 0.06 µmol/90 min silica). There wasno difference in eNOS protein between groups and eNOS mRNA wasnot detectable in either group, whereas silica exposure resultedin the appearance of both iNOS protein and mRNA. Silica exposureincreased CAT-1 and CAT-2 mRNA ~ 8-fold compared with controls.We conclude that the increase in NO production in silica-exposedlungs was associated with increased L-arg uptake from the vasculature,presumably resulting from increased CAT-1 and CAT-2, and by increasedL-arg metabolism viaarginase.

Comments

American Journal of Respiratory Cell and Molecular Biology, Volume 26, Number 3, pp 348-355 (March 2002). Permalink: http://ajrcmb.atsjournals.org/cgi/content/full/26/3/348