β3-肾上腺素能受体拮抗剂对心力衰竭大鼠模型心功能及内皮型一氧化氮合酶表达的影响

[Effect of beta3-adrenoceptor antagonist on the cardiac function and expression of endothelial nitric oxide synthase in a rat model of heart failure].

作者信息

Gan Run-tao, Li Wei-min, Wang Xu, Wu Shuang, Kong Yi-hui

机构信息

Department of Cardiology, The First Clinical College of Harbin Medical University, Harbin 150001, Heilongjiang, China.

出版信息

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2007 Nov;19(11):675-8.

PMID:17996136

Abstract

OBJECTIVE

To investigate the effect of beta(3)-adrenoceptor (beta(3)-AR) antagonist (SR59230A) on the cardiac function and left ventricular remodeling in a rat model of heart failure induced by isoproterenol (ISO), and to probe into its mechanism.

METHODS

Eight rats were randomly selected to serve as controls from 85 male adult Wistar rats. After a heart failure model was reproduced, twenty remain rats were randomly divided into ISO group (n = 10) and SR59230A group (SR group, n = 10). ISO group received intraperitoneal injection of 1 ml saline twice a day; SR group received intraperitoneal injection of 85 nmol SR59230A in 1 ml saline twice a day; control group received no treatment. The parameters determined included echocardiogram, the expression of nitric oxide synthase (eNOS) of left ventricle by the technique of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, cyclic guanosine monophosphate (cGMP) level by enzyme linked immunosorbent assay (ELISA), the ratio of left ventricular weight and body weight (LVW/BW), and the ratio of lung weight and body weight (PW/BW).

RESULTS

Compared with control group, the left ventricular end systolic pressure (LVESP), the maximum and minimum first derivative of left ventricular pressure (+/-dp/dtmax) were significantly decreased (all P<0.01), while heart rate (HR) and left ventricular end-diastolic pressure (LVEDP) were significantly increased (both P<0.01) in ISO group. Compared with ISO group, LVESP, +/-dp/dtmax were markedly higher (P<0.05 or P<0.01) respectively, whereas HR and LVEDP were markedly lower (P<0.05 and P<0.01) in SR group, and there was no difference in HR between SR group and control group (P>0.05), while LVEDP was higher in RS group than control group (P<0.01). The levels of eNOS mRNA, protein and cGMP were significantly lower in SR group compared with ISO group (all P<0.01). In addition, when compared with ISO group, LVW/BW ratio and PW/BW ratio in SR group were also decreased (both P<0.05).

CONCLUSION

beta(3)-AR antagonist SR59230A can block the beta(3)-AR-NOS-cGMP pathway and improve cardiac function in heart failure in rat when if is administered for a long term. SR59230A can also improve left ventricular remodeling in a certain degree.

摘要

目的

探讨β₃-肾上腺素能受体（β₃-AR）拮抗剂（SR59230A）对异丙肾上腺素（ISO）诱导的大鼠心力衰竭模型心功能及左心室重构的影响，并探讨其作用机制。

方法

从85只成年雄性Wistar大鼠中随机选取8只作为对照组。复制心力衰竭模型后，将剩余的20只大鼠随机分为ISO组（n = 10）和SR59230A组（SR组，n = 10）。ISO组每天腹腔注射1 ml生理盐水2次；SR组每天腹腔注射1 ml含85 nmol SR59230A的生理盐水2次；对照组不做处理。测定的参数包括超声心动图、采用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测左心室一氧化氮合酶（eNOS）的表达、采用酶联免疫吸附测定（ELISA）法检测环磷酸鸟苷（cGMP）水平、左心室重量与体重之比（LVW/BW）以及肺重量与体重之比（PW/BW）。

结果

与对照组相比，ISO组左心室收缩末期压力（LVESP）、左心室压力的最大和最小一阶导数（±dp/dtmax）显著降低（均P<0.01），而心率（HR）和左心室舒张末期压力（LVEDP）显著升高（均P<0.01）。与ISO组相比，SR组的LVESP、±dp/dtmax分别显著升高（P<0.05或P<0.01），而HR和LVEDP显著降低（P<0.05和P<0.01），且SR组与对照组的HR无差异（P>0.05），但SR组的LVEDP高于对照组（P<0.01）。与ISO组相比，SR组的eNOS mRNA、蛋白及cGMP水平均显著降低（均P<0.01）。此外，与ISO组相比，SR组的LVW/BW比值和PW/BW比值也降低（均P<0.05）。