N^G-硝基-L-精氨酸甲基酯对心力衰竭大鼠应用β_3受体激动剂后血流动力学和β受体mRNA表达水平的影响  

Effects of N^G-nitro-L-arginine methyl ester on hemodynamics and β-adrenoreceptors mRNA in rats with heart failure after β_3-adrenergic receptors agonist injection

作　　者：李为民[1] 孔一慧[1] 薛竟宜[1] 田颖[1] 

机构地区：[1]哈尔滨医科大学第一临床医学院心内科,150001

出　　处：《中华心血管病杂志》2005年第6期509-512,共4页Chinese Journal of Cardiology

基　　金：黑龙江省卫生厅资助项目(2002-036);黑龙江省教育厅资助项目(10551171)

摘　　要：目的研究不同剂量NG-硝基-L-精氨酸甲基酯(L-NAME)作用于心力衰竭(心衰)大鼠应用β3受体激动剂BRL37344(BRL)后的血流动力学、环-磷酸鸟苷(cGMP)含量和β受体mRNA表达水平,进一步明确β3受体在心衰中的作用途径和L-NAME的作用特点。方法将大鼠随机分为对照组(Ⅰ组)、异丙肾上腺素(Iso)组(Ⅱ组)、Iso+BRL组(Ⅲ组)、Iso+BRL+L-NAME低剂量组(5mg/kg体重,Ⅳ组)、Iso+BRL+L-NAME中剂量组(50mg/kg体重,Ⅴ组)、Iso+BRL+L-NAME高剂量组(100mg/kg体重,Ⅵ组)。测定(1)血流动力学:左室舒张末压(LVEDP),左室收缩末压(LVESP),左室压力最大上升、下降速率(±dp/dt)。(2)心肌cGMP含量。(3)心肌组织β1、β2、β3受体mRNA水平。结果①Ⅱ组较Ⅰ组±dp/dt绝对值、LVESP明显降低,LVEDP明显升高(除-dp/dtP<0.05,余均为P<0.01);Ⅲ组较Ⅱ组-dp/dt绝对值、LVESP明显下降,LVEDP明显升高(P<0·05),+dp/dt变化呈下降趋势,但差异无统计学意义;随着L-NAME剂量的增加,±dp/dt绝对值升高,LVEDP降低,但大剂量L-NAME应用后,血流动力学又有恶化倾向。②Ⅰ、Ⅱ、Ⅲ组cGMP水平呈逐渐上升趋势(均为P<0.01),应用L-NAME后随着剂量的增加Ⅳ、Ⅴ、Ⅵ组cGMP呈下降趋势,大剂量应用L-NAME后cGMP回到正常对照组水平。③Ⅰ、Ⅱ、Ⅲ组比较,β1受体mRNA/β-actinmRNA为Ⅰ组最高、Ⅲ组最低,差异有统计学意义(均为P<0.01);β2受体mRNA/β-actinmRNA呈下降趋势,但三组间差异无统计学意义;而β3受体mRNA/β-actinmRNA的三组中Ⅲ组最高、Ⅰ组最低,差异有统计学意义(均为P<0.01);而Ⅳ、Ⅴ、Ⅵ组三种β受体mRNA水平与Ⅲ组相似,差异无统计学意义。结论β3受体经NOS途径发挥作用,L-NAME可部分阻断β3受体激动剂对衰竭心脏的负性肌力作用,改善心功能,但大剂量应用会加重心衰进程。Objective To evaluate the effects of different doses of N G-nitro-L-arginine methyl ester (L-NAME) on hemodynamics , cyclic guanosine monophosphate(cGMP) production and the level of β-adrenergic receptors (β-ARs) mRNA in a heart failure rat model after BRL-37344(β_3- ARs agonist) injection. Meanwhile,to investigate the influence of β_3-ARs and L-NAME on signal transduction in failing heart. Methods The rats were randomly divided into six groups, control group (group Ⅰ), Iso (isoproterenol) group(group Ⅱ), Iso+BRL group (group Ⅲ), Iso+BRL+ low dose of L-NAME group(5 mg/kg, group Ⅳ),Iso+BRL+ moderate dose of L-NAME group (50 mg/kg, group Ⅴ),Iso+BRL+ high dose of L-NAME group(100 mg/kg, group Ⅵ). The hemodynamics [left ventricular end systolic pressure (LVESP),±dp/dt, left ventricular end diastolic pressure (LVEDP)], cardiac cGMP and the levels of β_ 1- ,β_ 2- , and β_ 3- ARs mRNA were measured. Results (1)LVESP,±dp/dt values in group Ⅱ were significantly lower, and LVEDP was significantly higher than that in groupⅠ(except -dp/dt P < 0.05,the rest were P < 0.01). Comparing with group Ⅱ, group Ⅲ had lower -dp/dt value and LVESP, higher LVEDP( P < 0.05). The level of +dp/dt had a trend to be lower but lacked statistical significance between two groups . The value of ±dp/dt got higher and LVEDP got lower along with higher dose of L-NAME , but a large dose of L-NAME had more deteriorated cardiac functions. (2)The cardiac cGMP in groupⅠ, Ⅱ and Ⅲ had a higher tendency( P <0.01). The tendency of cardiac cGMP in group Ⅳ,Ⅴand Ⅵ was inversed with the dose of L-NAME . After a large dose of L-NAME was applied, cGMP returned to the same level as Group Ⅰ .(3)Among groups Ⅰ, Ⅱand Ⅲ, the level of β_1-AR mRNA was the highest in group Ⅰ and the lowest in group Ⅲ( P <0.01). The levels of β_2-AR mRNA were also tended to be lower among three groups but with no significance. While the level of β_3-AR mRNA was the highest in group Ⅲ.The levels of β-AR mRNA were all the same in gr

关 键 词：N^G-硝基-L-精氨酸甲基酯 心力衰竭 大鼠 Β3受体 激动剂 血流动力学 mRNA 

分 类 号：R541.6[医药卫生—心血管疾病]