Portnychenko Alla G, Harmatina Olga Yu, Kotsuruba Anatolij V, Moybenko Oleksij O
Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine;
Exp Clin Cardiol. 2005 Winter;10(4):223-8.
To determine the participation of inducible nitric oxide synthase (iNOS) in cardiodepressive phenomena during late preconditioning caused by subtoxic doses of lipopolysaccharide (LPS).
Spontaneously beating hearts isolated from male Wistar rats (350 g to 400 g), intact or preconditioned with LPS (0.25 mg/kg given intraperitoneally 18 h before heart excision), were used to measure contractile performance during 30 min of ischemia and 40 min of reperfusion in the Langendorff mode. For selective iNOS blockade, hearts were perfused with phenylene-1,3-bis(ethane-2-isothiourea) (50 nmol/L). Expression of iNOS (determined using Western blotting) and NOS activities were determined in frozen myocardial tissues.
Subtoxic doses of LPS caused iNOS induction in the heart and depression of contractile function, but improved heart postischemic recovery. In all groups of animals, expression of iNOS was higher in the right than left ventricles. Ischemia and postischemic reperfusion of intact heart intensified production of nitric oxide (NO), predominantly by iNOS. The preconditioning led to iNOS activation during ischemia in the left ventricle and iNOS depression in the right ventricle, owing to feedback caused by the initially higher iNOS expression and activity in the right ventricle. Postischemic reperfusion diminished NOS activities in preconditioned myocardial tissues. Blockade of iNOS significantly slowed preconditioned heart recovery and partially restored left ventricular developed pressure, but only after 20 min of reperfusion.
iNOS-produced NO plays a role in the development of delayed cardioprotection and cardiodepressive effects (in part) after extravasal administration of a minimal dose of endotoxin.
确定诱导型一氧化氮合酶（iNOS）在亚毒性剂量脂多糖（LPS）引起的晚期预处理期间心脏抑制现象中的作用。
从雄性Wistar大鼠（350 g至400 g）分离出的自主跳动心脏，完整的或用LPS预处理（在心脏切除前18小时腹腔注射0.25 mg/kg），用于在Langendorff模式下测量30分钟缺血和40分钟再灌注期间的收缩性能。为了选择性阻断iNOS，心脏用亚苯基-1,3-双（乙烷-2-异硫脲）（50 nmol/L）灌注。在冷冻心肌组织中测定iNOS的表达（使用蛋白质印迹法测定）和NOS活性。
亚毒性剂量的LPS导致心脏中iNOS的诱导和收缩功能的抑制，但改善了心脏缺血后的恢复。在所有动物组中，iNOS的表达在右心室中高于左心室。完整心脏的缺血和缺血后再灌注增强了一氧化氮（NO）的产生，主要由iNOS产生。预处理导致左心室缺血期间iNOS激活，右心室中iNOS抑制，这是由于右心室中最初较高的iNOS表达和活性引起的反馈。缺血后再灌注降低了预处理心肌组织中的NOS活性。阻断iNOS显著减慢了预处理心脏的恢复，并部分恢复了左心室舒张末压，但仅在再灌注20分钟后。
iNOS产生的NO在小剂量内毒素血管外给药后延迟心脏保护和心脏抑制作用（部分）的发展中起作用。
