L-lysine decreases nitric oxide production and increases vascular resistance in lungs isolated from lipopolysaccharide-treated neonatal pigs.
Nitric oxide (NO) production may depend on the uptake of L-arginine (L-arg), the substrate for NO synthase in inflammatory lung diseases. The cellular transport of L-arg occurs via the cationic amino acid transporters (CAT), and L-lysine (L-lys) competitively inhibits CAT. Neonatal pigs were treated with lipopolysaccharide (LPS) or vehicle for 4 h. LPS increased exhaled NO (exNO; 0.026 +/- 0.003 to 0.046 +/- 0.003 nmol. kg(-1). min(-1); p < 0.005) and decreased mean systemic arterial blood pressure (89 +/- 4 to 67 +/- 4 mm Hg; p < 0.05), whereas vehicle did not affect exNO or mean systemic arterial blood pressure. The lungs were then isolated and perfused; exNO was greater in lungs from LPS-treated animals (0.08 +/- 0.01 nmol/kg/min) than in lungs from vehicle-treated animals (0.05 +/- 0.01 nmol. kg(-1). min(-1); p < 0.05). The addition of L-arg (0.3 mM) significantly (p < 0.05) increased exNO production in both groups of lungs (mean increase 0.04 +/- 0.01 nmol. kg(-1). min(-1) LPS-treated lungs, p < 0.05; mean increase 0.02 +/- 0.01 nmol. kg(-1). min(-1) vehicle-treated lungs); however, L-arg decreased pulmonary vascular resistance (PVR) only in LPS-treated lungs (mean decrease 0.03 +/- 0.01 mm Hg. ml(-1). kg(-1). min(-1), p < 0.05). L-lys caused a dose-dependent decrease in exNO production and a dose-dependent increase in PVR in LPS-treated lungs. L-lys decreased exNO only at 30 mM and had no effect on PVR in vehicle-treated lungs. In four lungs each from vehicle- and LPS-treated animals, reverse transcriptase-PCR demonstrated CAT-2 mRNA only in LPS-treated animals. These results suggest that the increased NO production in the lungs from LPS-treated animals depends on the uptake of vascular L-arg.
Carter
Barney W
BW
Vascular Physiology Group, Department of Pediatrics, University of New Mexico HSC, Albuquerque 87131, USA.
Chicoine
Louis G
LG
Nelin
Leif D
LD
D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D027202:Cationic Amino Acid Transporter 2 / Q000235:genetics; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008239:Lysine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D010477:Perfusion; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects*
D027202:Cationic Amino Acid Transporter 2; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; D008239:Lysine