一氧化氮合酶抑制物对大鼠离体乳头肌收缩力的影响及其机制  

Effects of nitric oxide synthase inhibitors on the contractility of rat isolated papillary muscles and their mechanisms of action

作　　者：聂凡[1,2] 宜全[2] 张贵平[2] 罗健东[2] 熊燕[1,2] 

机构地区：[1]广州医学院蛇毒研究所,广州510182 [2]广州医学院药理教研室,广州510182

出　　处：《国际病理科学与临床杂志》2012年第1期1-7,共7页Journal of International Pathology and Clinical Medicine

基　　金：国家自然科学基金(30873062)~~

摘　　要：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 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.

关 键 词：非对称二甲基精氨酸 一氧化氮合酶 乳头肌 收缩力 大鼠 

分 类 号：R363[医药卫生—病理学]