Maintaining nitric oxide-induced airway relaxation with superoxide dismutase
2007 (English)In: Nitric oxide, ISSN 1089-8603, E-ISSN 1089-8611, Vol. 16, no 4, 419-424 p.Article in journal (Refereed) Published
We have previously shown that the protective effect of inhaled nitric oxide (iNO) against methacholine-induced bronchoconstriction is negated in airways subjected to hyperosmotic stress. In this study, hypothesizing that the impaired efficiency of iNO was caused by release of reactive oxygen radicals, we examined the effect of the radical scavenging enzyme superoxide dismutase (SOD).
Hemodynamic and respiratory measurements were performed on anesthetized rabbits after (1) inhalation of methacholine (MCh), (2) iNO (80 ppm), followed by MCh, (3) inhalation of hypertonic saline (HS), followed by iNO and MCh and (4) pre-treatment with inhalation of SOD, followed by HS, iNO and MCh. We analyzed plasma for a marker of oxidative stress, 8-iso-prostaglandin (PG)F2α and for a marker of activation of COX-mediated inflammatory cascades, PGF2α metabolite.
Pre-treatment with SOD restored the bronchoprotective response to iNO in hyperosmotic airways. No direct effect was seen by SOD treatment on levels of 8-iso-PGF2α, but this marker of oxidative stress correlated positively with increased bronchoconstriction. Hyperosmotic challenge elevated levels of PGF2α metabolite, and pre-treatment with SOD protected against this activation of the inflammatory cascade.
SOD pre-treatment restores the relaxant effects of iNO in hyperosmotically challenged airways by attenuating oxidative stress and activation of COX-mediated inflammatory cascades.
Place, publisher, year, edition, pages
2007. Vol. 16, no 4, 419-424 p.
Administration; Inhalation, Animals, Biological Markers/blood, Bronchoconstriction/*drug effects, Bronchodilator Agents/*pharmacology, Dinoprost/analogs & derivatives/blood, Female, Methacholine Chloride/pharmacology, Nitric Oxide/*pharmacology, Oxidative Stress/drug effects, Rabbits, Signal Transduction/drug effects, Superoxide Dismutase/blood/*pharmacology
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-16048DOI: 10.1016/j.niox.2007.03.003ISI: 000247271600004PubMedID: 17459737OAI: oai:DiVA.org:uu-16048DiVA: diva2:43819