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lHz、波宽5ms)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(asymmetricdimethylarginine,ADMA)孵育乳头肌60min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N(-^G)硝基-L-精氨酸孵育60min,均可产生与ADMA相似的抑制作用。用1mmol/L一氧化氮(NO)合成前体L一精氨酸或10μmol/LNO供体硝普钠预孵育肌条15min,再与ADMA共孵育60min,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 effects and underlying mechanisms of nitric oxide synthase (NOS) inhibitors on contractility of rat papillary muscles response to electrical stimulation.Methods: The left ventricular papillary muscles were isolated from Sprague Dawley rats, and the contraction tension of papillary muscles elicited by electrical stimulation was recorded by the Muscle Research System. Results: After incubation of rat papillary muscles with 30 μmol/L endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) for 60 rain, the contraction tension of papillary muscles elicited by electrical stimulation was significantly decreased compared with control group. Similarly, the exogenous NOS inhibitorj NC-nitro-L-arginine had a similar effect on the contraction tension of papillary muscles. When rat papillary muscles were pretreated with both 1 mmol/L nitric oxide (NO) precursor L-arginine and 10 μmol/L NO donor sodium nitroprusside for 15 min, followed by co- incubation with ADMA for 60 min, the inhibition of contraction tension induced by ADMA could be reversed.Furthermore, pretreatment with either 10 [tmol/L protein kinases C (PKC) inhibitor chelerythrine or anti-oxidant N-acetyl-L-cysteine also abolished the negative inotropic effect of ADMA on the isolated rat papillary muscles. Conclusion: Either endogenous or exogenous inhibitors of NOS exerts a negative inotropic effect on isolated rat papillary muscles, which may be due to the decrease of NO production, activation of PKC, and the increase of oxidative stress in papillary muscles.