title: Absence of inducible nitric oxide synthase reduces myocardial damage during ischemia reperfusion in streptozotocin-induced hyperglycemic mice.
abstract: We investigated the role of inducible nitric oxide synthase (iNOS) on ischemic myocardial damage and angiogenic process in genetically deficient iNOS (iNOS(-/-)) mice and wild-type littermates (iNOS(+/+)), with and without streptozotocin-induced (70 mg/kg intravenously) diabetes. After ischemia (25 min) and reperfusion (120 min), both iNOS(+/+) and iNOS(-/-) diabetic mice (blood glucose 22 mmol/l) had myocardial infarct size greater than their respective nondiabetic littermates (P < 0.01). Myocardial infarct size (P < 0.05), apoptotic index (P < 0.005), and tissue levels of tumor necrosis factor (P < 0.01), interleukin-6 (P < 0.01), and interleukin-18 (P < 0.01) were higher in nondiabetic iNOS(-/-) mice compared with nondiabetic iNOS(+/+) mice. As compared with diabetic iNOS(-/-) mice, diabetic iNOS(+/+) mice showed a greater infarct size (P < 0.01) associated with the highest tissue levels of nitrotyrosine and proinflammatory cytokines, as well as apoptosis. The beneficial role of iNOS in modulating defensive responses against ischemia/reperfusion injury seems to be abolished in diabetic mice.
authors.affiliation: Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy. raffaele.marfella@unina2.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Marfella
authors.forename: Clara
authors.initials: C
authors.lastname: Di Filippo
authors.forename: Katherine
authors.initials: K
authors.lastname: Esposito
authors.forename: Francesco
authors.initials: F
authors.lastname: Nappo
authors.forename: Elena
authors.initials: E
authors.lastname: Piegari
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Liberato
authors.initials: L
authors.lastname: Berrino
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.forename: Dario
authors.initials: D
authors.lastname: Giugliano
authors.forename: Michele
authors.initials: M
authors.lastname: D'Amico
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D006943:Hyperglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values; D013311:Streptozocin; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007378:Interleukins; C002744:3-nitrotyrosine; D014443:Tyrosine; D013311:Streptozocin; D012313:RNA; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse