Zhang Kun, Li Yi-Fan, Patel Kaushik P
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, Nebraska 68198-4575, USA.
Am J Physiol Regul Integr Comp Physiol. 2002 Apr;282(4):R1006-15. doi: 10.1152/ajpregu.00241.2001.
One characteristic of heart failure (HF) is increased sympathetic activation. The paraventricular nucleus (PVN) of the hypothalamus (involved in control of sympathetic outflow) has been shown to have increased neuronal activation during HF. This study examined the influence of endogenous GABA input (inhibitory in nature) into the PVN on renal sympathetic nerve discharge (RSND), arterial blood pressure (BP), and heart rate (HR) in rats with HF induced by coronary artery ligation. In alpha-chloralose- and urethane-anesthetized rats, microinjection of bicuculline (a GABA antagonist) into the PVN produced a dose-dependent increase in RSND, BP, and HR in both sham-operated control and HF rats. Bicuculline attenuated the increase in RSND and BP in HF rats compared with control rats. Alternatively, microinjection of the GABA agonist muscimol produced a dose-dependent decrease in RSND, BP, and HR in both control and HF rats. Muscimol was also less effective in decreasing RSND, BP, and HR in HF rats than in control rats. These results suggest that endogenous GABA-mediated input into the PVN of rats with HF is less effective in suppressing RSND and BP compared with control rats. This is partly due to the post-release actions of GABA, possibly caused by altered function of post-synaptic GABA receptors in the PVN of rats with HF. Reduced GABA-mediated inhibition in the PVN may contribute to increased sympathetic outflow, which is commonly observed during HF.
心力衰竭（HF）的一个特征是交感神经激活增强。下丘脑室旁核（PVN）（参与交感神经输出的控制）已被证明在HF期间神经元激活增加。本研究探讨了内源性GABA输入（本质上具有抑制作用）进入PVN对冠状动脉结扎诱导的HF大鼠肾交感神经放电（RSND）、动脉血压（BP）和心率（HR）的影响。在α-氯醛糖和乌拉坦麻醉的大鼠中，向PVN微量注射荷包牡丹碱（一种GABA拮抗剂）在假手术对照大鼠和HF大鼠中均引起RSND、BP和HR的剂量依赖性增加。与对照大鼠相比，荷包牡丹碱减弱了HF大鼠RSND和BP的增加。另外，向PVN微量注射GABA激动剂蝇蕈醇在对照大鼠和HF大鼠中均引起RSND、BP和HR的剂量依赖性降低。蝇蕈醇在降低HF大鼠RSND、BP和HR方面也比对照大鼠效果差。这些结果表明，与对照大鼠相比，内源性GABA介导的输入进入HF大鼠的PVN在抑制RSND和BP方面效果较差。这部分是由于GABA的释放后作用，可能是由HF大鼠PVN中突触后GABA受体功能改变引起的。PVN中GABA介导的抑制作用减弱可能导致交感神经输出增加，这在HF期间很常见。
