title: Effects of iNOS-related NO on hearts exposed to liposoluble iron.
abstract: Inducible nitric oxide synthase (iNOS) protects heart against ischemia/reperfusion injury. However, it is unknown whether the beneficial effects of iNOS are mediated by the interaction of NO with radical oxygen species (ROS). To address this issue, we examined the effects of liposoluble iron-induced ROS generation in isolated perfused hearts from rats treated with lipopolysaccharide (LPS). LPS administration (10 mg/kg, i.p., 6 h before heart removal) induced iNOS expression and increased NO production as indicated by a 3-fold elevation of nitrite level in coronary effluents relative to control hearts. An enhanced expression of hemeoxygenase 1 protein was also observed in septic hearts compared to control. Iron-induced perfusion and contractile deficits were ameliorated by LPS with more important coronary than myocardial benefits. In iron-loaded hearts, oxidative stress as measured by the 2,3 dihydroxybenzoic acid/salicylic acid concentration ratio in cardiac tissue was 23% lower in septic than in control heart although the difference did not reach significance. In addition, the presence of the NO synthase inhibitor N-nitro-L-arginine in the perfusion medium totally blocked NO production but did not reverse the protective effects of LPS. The results indicate that LPS protects from iron-induced cardiac dysfunction by mechanisms independent on ex vivo NO production and suggest that NO acts as a trigger rather than a direct mediator of the cardioprotective effects of LPS in heart exposed to iron.
authors.affiliation: Laboratoire de Pharmacodynamie et Physiologie Pharmaceutique Faculté de Pharmacie, BP 87900, 21079 Dijon Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Mossiat
authors.forename: C
authors.initials: C
authors.lastname: Demougeot
authors.forename: A
authors.initials: A
authors.lastname: Prigent-Tessier
authors.forename: N
authors.initials: N
authors.lastname: Bertrand
authors.forename: P
authors.initials: P
authors.lastname: Garnier
authors.forename: A
authors.initials: A
authors.lastname: Beley
authors.forename: C
authors.initials: C
authors.lastname: Marie
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical; D015151:Immunoblotting; D007501:Iron / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology*; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D019335:Nitroarginine / Q000737:chemistry; D018384:Oxidative Stress; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control; D020156:Salicylic Acid / Q000378:metabolism; D013997:Time Factors
chemical_list: D062385:Hydroxybenzoates; D008070:Lipopolysaccharides; D009573:Nitrites; D019335:Nitroarginine; D009569:Nitric Oxide; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D001120:Arginine; D007501:Iron; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D020156:Salicylic Acid