慢性心衰大鼠延髓头端腹外侧区GABA_B受体介导的心血管效应

Cardiovascular effects mediated by GABA_B receptor in the rostral ventrolateral medulla of chronic heart failure rats

为证实慢性心衰大鼠延髓头端腹外侧区(RVLM)γ-氨基丁酸B型(GABAB)受体介导的交感神经紧张性抑制作用,采用冠脉结扎法诱导大鼠慢性心衰,在延髓头端腹外侧区微量注射GABAB受体阻断剂CGP-35348,观察动脉血压和心率的变化.结果表明:假手术组和心衰组大鼠心率、血压均有升高,但心衰组升高幅度与假手术组相比显著减小(P<0.05).假手术组和心衰大鼠RVLM微量注射GABAB受体激动剂巴氯芬均导致心率、血压下降,但心衰组下降幅度与假手术组相比显著减小(P<0.05).以Western blot实验法观察延髓头端腹外侧区内GABAB受体蛋白表达量变化,与假手术组相比,心衰组大鼠RVLM内GABAB受体表达下调(P<0.05).说明心衰大鼠延髓头端腹外侧区GABAB受体中介的紧张抑制作用发生钝化,其机制可能与延髓头端腹外侧区内GABAB受体表达下调有关.

The goal of this study was to determine the role of ？,-aminobutyric acid B-type receptor （GABAB） in mediating the tonic inhibitory influence on the rostral ventrolaterl medulla （RVLM） in rats with heart failure（HF）. HF animal model was induced by coronary artery ligation. Unilateral mieroinjection of GABAB receptor antagonist CGP-35348 into the RVLM produced a dose-dependent increase in blood pressure（BP） and heart rate（HR） in both sham and HF rats. There was a blunted increase in these parameters in HF rats compared with the sham rats. Alternatively, mieroinjeetion of the GABAB receptor agonist baclofen into the RVLM produeed a dose-dependent decrease in BP and HR in both sham and HF rats,baclofen also less effective in decreasing BP and HR in HF rat than in sham rat. The results of Western blot show that GABAB receptor protein expression levels in the RVLM were significantly decreased in HF rats compared with sham rats. The results indicate that GABAB receptor mediates the tonic inhibitory influence on RVLM is blunted and the mechanism may be involved in the downregulation of GABAB receptor in RVLM.