title: Antibacterial peptide PR-39 affects local nitric oxide and preserves tissue oxygenation in the liver during septic shock.
abstract: The effects of the antibacterial peptide PR-39 on nitric oxide (NO) and liver oxygenation (pO(2)) in a mouse model of endotoxaemia have been explored. In vivo electron paramagnetic resonance (EPR) spectroscopy was used to make direct measurements of liver NO and pO(2). Measurements of pO(2) were made at two different anatomical locations within hepatic tissue to assess effects on blood supply (hence oxygen supply) and lobule oxygenation; selectively from the liver sinusoids or an average pO(2) across the liver lobule. PR-39 induced elevated levels of liver NO at 6 h following injection of lipopolysaccharide (LPS) as a result of increased iNOS expression in liver, but had no effect on eNOS or circulatory NO metabolites. Sinusoidal oxygenation was preserved, and pO(2) across the hepatic tissue bed improved with PR-39 treatment. We propose that the beneficial effects of PR-39 on liver in this septic model were mediated by increased levels of local NO and preservation of oxygen supply to the liver sinusoids.
authors.affiliation: Department of Cardiology, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Melanie
authors.initials: M
authors.lastname: Madhani
authors.forename: Aaron
authors.initials: A
authors.lastname: Barchowsky
authors.forename: Linda
authors.initials: L
authors.lastname: Klei
authors.forename: Chris R
authors.initials: CR
authors.lastname: Ross
authors.forename: Simon K
authors.initials: SK
authors.lastname: Jackson
authors.forename: Harold M
authors.initials: HM
authors.lastname: Swartz
authors.forename: Philip E
authors.initials: PE
authors.lastname: James
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen / Q000032:analysis; D010101:Oxygen Consumption; D012039:Regional Blood Flow; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D016328:NF-kappa B; C072212:PR 39; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D010100:Oxygen