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目的:探讨一氧化氮合酶(NOS)抑制物对电刺激大鼠离体左心室乳头肌收缩力的影响及其机制。方法:制备大鼠离体左心室乳头肌条,用Muscle Research System记录电刺激(频率1 Hz、波宽5 ms)诱导心肌收缩张力。结果:与正常对照组比较,用30μmol/L内源性NOS抑制物非对称二甲基精氨酸(asymmetric dimethylarginine,ADMA)孵育乳头肌60 min后,肌条对电刺激收缩张力明显降低;用相同浓度的外源性NOS抑制物NG-硝基-L-精氨酸孵育60 min,均可产生与ADMA相似的抑制作用。用1 mmol/L一氧化氮(NO)合成前体L-精氨酸或10μmol/L NO供体硝普钠预孵育肌条15 min,再与ADMA共孵育60 min,均可逆转ADMA对心肌收缩的抑制作用。用10μmol/L蛋白激酶C抑制剂chelerythrine或抗氧化剂N-乙酰半胱氨酸预处理,亦可逆转ADMA的抑制作用。结论:NOS抑制物对电刺激大鼠离体左心室乳头肌收缩具有抑制作用,可能是由于减少NO生成、活化蛋白激酶C、使氧化应激增加所致。
Objective: To investigate the effect and mechanism of nitric oxide synthase (NOS) inhibitors on contractile force of isolated left ventricular papillary muscles in rats. METHODS: Isolated rat left ventricular papillary muscle strips were prepared and the myocardial contractile tension induced by electrical stimulation (frequency 1 Hz and wave width 5 ms) was recorded by Muscle Research System. RESULTS: Compared with the normal control group, the contractile tension of muscle strips on electrical stimulation was significantly decreased after incubation of papillary muscles with asymmetric dimethylarginine (ADMA) at a concentration of 30 μmol / L for 60 min. The same concentration of exogenous NOS inhibitor NG-nitro-L-arginine incubated 60 min, can produce ADMA similar inhibition. The preincubation of muscle strips with 1 mmol / L nitric oxide (NO) precursor L-arginine or 10 μmol / L NO donor sodium nitroprusside for 15 min and then incubated with ADMA for 60 min both reversed the effect of ADMA on cardiac myocytes Shrinkage inhibition. Pretreatment with 10 micromol / L protein kinase C inhibitor chelerythrine or the antioxidant N-acetylcysteine also reversed the inhibitory effect of ADMA. CONCLUSIONS: NOS inhibitors inhibit the contractile activity of isolated left ventricular papillary muscles in rats, which may be due to the reduction of NO production and activation of protein kinase C, resulting in increased oxidative stress.