title: Mechanisms underlying growth hormone effects in augmenting nitric oxide production and protein tyrosine nitration during endotoxin challenge.
abstract: The present study defined the effects of GH administration on components of the nitric oxide (NO)-generating cascade to account for observed increases in NO production and protein nitration after an immune challenge. Calves were assigned to groups with or without GH treatment (100 microg GH/kg body weight or placebo im, daily for 12 d) and with or without low-level endotoxin [lipopolysaccharide (LPS), 2.5 microg/kg, or placebo, iv]. Plasma was obtained for estimation of NO changes as [NO(2)(-) + NO(3)(-)] (NO(x)). Transcutaneous liver biopsies were collected for measurement of protein tyrosine nitration, cationic amino acid transporter (CAT)-2 mRNA transporter, and constitutive NO synthase (cNOS), inducible NOS (iNOS), and arginase activity. Liver protein nitration increased more than 10-fold 24 h after LPS and an additional 2-fold in animals treated with GH before LPS. GH increased plasma NO(x) after LPS to levels 27% greater than those measured in non-GH-treated calves. LPS increased CAT-2 mRNA after LPS; GH was associated with a 24% reduction in CAT-2 mRNA content at the peak time response. cNOS activity was 3-fold greater than iNOS after LPS. NOS activities were increased 140% (cNOS) at 3 h and 169% (iNOS) at 6 h, respectively, after LPS; GH treatment increased cNOS activity and the phosphorylation of endothelial NOS after LPS more than 2-fold over that measured in non-GH-treated calves. The data suggest that an increased production of nitrated protein develops in the liver during low-level, proinflammatory stress, and nitration is increased by GH administration through a direct effect on the competing activities of NOS and arginase, modulatable critical control points in the proinflammatory cascade.
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Growth Biology Laboratory, B-200, Room 201, Beltsville Agricultural Research Center-East, Beltsville, Maryland 20705, USA. elsasser@anri.barc.usda.gov.
authors.forename: Ted H
authors.initials: TH
authors.lastname: Elsasser
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Kahl
authors.forename: Carol
authors.initials: C
authors.lastname: MacLeod
authors.forename: Benjamin
authors.initials: B
authors.lastname: Nicholson
authors.forename: James L
authors.initials: JL
authors.lastname: Sartin
authors.forename: Congjun
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D027202:Cationic Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D015870:Gene Expression / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009584:Nitrogen / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014443:Tyrosine / Q000378:metabolism
chemical_list: D027202:Cationic Amino Acid Transporter 2; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D014443:Tyrosine; D013006:Growth Hormone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D001119:Arginase; D009584:Nitrogen