Antibacterial peptide PR-39 affects local nitric oxide and preserves tissue oxygenation in the liver during septic shock

Research output: Contribution to journalArticle

Authors

  • Aaron Barchowsky
  • Linda Klei
  • Chris R Ross
  • Simon K Jackson
  • Harold M Swartz
  • Philip E James

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)232-40
Number of pages9
JournalBiochimica et Biophysica Acta
Volume1588
Issue number3
Publication statusPublished - 12 Dec 2002

Keywords

  • Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Disease Models, Animal, Lipopolysaccharides, Liver, Male, Mice, Mice, Inbred BALB C, NF-kappa B, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Oxygen, Oxygen Consumption, Regional Blood Flow, Shock, Septic, Time Factors