L-Arginine uptake and metabolism following in vivo silica exposure in rat lungs.
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 [(3)H]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 micromol/90 min control, 1.77 +/- 0.06 micromol/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 approximately 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.
Nelin
Leif D
LD
Vascular Physiology Group and Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA. lnelin@salud.unm.edu
Krenz
Gary S
GS
Chicoine
Louis G
LG
Dawson
Christopher A
CA
Schapira
Ralph M
RM
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D027201:Cationic Amino Acid Transporter 1 / Q000378:metabolism; D027202:Cationic Amino Acid Transporter 2 / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000633:toxicity*
D027201:Cationic Amino Acid Transporter 1; D027202:Cationic Amino Acid Transporter 2; D009569:Nitric Oxide; D012822:Silicon Dioxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat