Reactive oxygen species (ROS) and nitric oxide (NO) modulate normal and septic skeletal muscle contractility and redox state. We evaluated the involvement of NO synthases (NOS) and heme oxygenases (HO) in nitrosative and oxidative stresses in sepsis-induced diaphragmatic contractile dysfunction. Sepsis was elicited by injecting rats and transgenic mice deficient in either inducible (iNOS) or neuronal (nNOS) isoforms with 20 mg/kg E. coli lipolysaccharide (LPS). Peroxynitrite formation was monitored by measuring nitrotyrosine immunoreactivity with selective antibodies. Oxidative stress was assessed by measuring protein oxidation (carbonyl groups), lipid peroxidation (hydoxynonenal protein adducts), and muscular glutathione concentrations. HO expression was evaluated using anti-HO-1 and -HO-2 antibodies, and biological significance using HO inhibitor, and contractility studies. We conclude that the iNOS isoform plays a major role in nitrotyrosine formation and protein oxidation in septic ventilatory muscles, and that HO protect muscle contractile machinery from the deleterious effects of ROS in control and septic muscles.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.32977 |
| Date | January 2001 |
| Creators | Barreiro, Esther. |
| Contributors | Hussain, Sabah N. A. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001838533, proquestno: MQ75287, Theses scanned by UMI/ProQuest. |
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