Mossiat C, Demougeot C, Prigent-Tessier A, Bertrand N, Garnier P, Beley A, Marie C
Laboratoire de Pharmacodynamie et Physiologie Pharmaceutique Faculté de Pharmacie, BP 87900, 21079 Dijon Cedex, France.
Free Radic Res. 2003 Jul;37(7):749-56. doi: 10.1080/1071576031000103050.
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.
诱导型一氧化氮合酶（iNOS）可保护心脏免受缺血/再灌注损伤。然而，iNOS的有益作用是否通过一氧化氮（NO）与活性氧（ROS）的相互作用介导尚不清楚。为解决这一问题，我们研究了脂溶性铁诱导的ROS生成对来自用脂多糖（LPS）处理的大鼠的离体灌注心脏的影响。LPS给药（10mg/kg，腹腔注射，在取心脏前6小时）诱导iNOS表达并增加NO生成，冠状动脉流出液中亚硝酸盐水平相对于对照心脏升高了3倍即表明了这一点。与对照相比，在脓毒症心脏中还观察到血红素加氧酶1蛋白表达增强。LPS改善了铁诱导的灌注和收缩功能障碍，对冠状动脉的益处比心肌更重要。在铁负荷的心脏中，尽管差异未达到显著水平，但脓毒症心脏中通过心脏组织中2,3-二羟基苯甲酸/水杨酸浓度比测量的氧化应激比对照心脏低23%。此外，灌注培养基中存在NO合酶抑制剂N-硝基-L-精氨酸完全阻断了NO生成，但并未逆转LPS的保护作用。结果表明，LPS通过独立于体外NO生成的机制保护心脏免受铁诱导的功能障碍，并表明NO在暴露于铁的心脏中作为LPS心脏保护作用的触发因素而非直接介质起作用。
