Ding Lei, Gao Run, Xiong Xiao-Qing, Gao Xing-Ya, Chen Qi, Li Yue-Hua, Kang Yu-Ming, Zhu Guo-Qing
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
PLoS One. 2015 Aug 28;10(8):e0136983. doi: 10.1371/journal.pone.0136983. eCollection 2015.
Chemical stimulation of white adipose tissue (WAT) induces adipose afferent reflex (AAR), and thereby causes a general sympathetic activation. Paraventricular nucleus (PVN) is important in control of sympathetic outflow. This study was designed to investigate the role of γ-aminobutyric acid (GABA) in PVN in regulating the AAR.
METHODOLOGY/PRINCIPAL FINDINGS: Experiments were carried out in anesthetized rats. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded. AAR was evaluated by the RSNA and MAP responses to electrical stimulation of the right epididymal WAT (eWAT) afferent nerve. Electrical stimulation of eWAT afferent nerve increase RSNA. Bilateral microinjection of the GABAA receptor agonist isoguvacine or the GABAB receptor agonist baclofen attenuated the AAR. The effect of isoguvacine on the AAR was greater than that of baclofen. The GABAA receptor antagonist gabazine enhanced the AAR, while the GABAB receptor antagonist CGP-35348 had no significant effect on the AAR. Bilateral PVN microinjection of vigabatrin, a selective GABA-transaminase inhibitor, to increase endogenous GABA levels in the PVN abolished the AAR. The inhibitory effect of vigabatrin on the AAR was attenuated by the pretreatment with gabazine or CGP-35348. Pretreatment with combined gabazine and CGP-35348 abolished the effects of vigabatrin.
Activation of GABAA or GABAB receptors in the PVN inhibits the AAR. Blockade of GABAA receptors in the PVN enhances the AAR. Endogenous GABA in the PVN plays an important role in regulating the AAR.
化学刺激白色脂肪组织（WAT）可诱发脂肪传入反射（AAR），进而引起全身交感神经激活。室旁核（PVN）在交感神经输出控制中起重要作用。本研究旨在探讨PVN中γ-氨基丁酸（GABA）在调节AAR中的作用。
方法/主要发现：实验在麻醉大鼠中进行。连续记录肾交感神经活动（RSNA）和平均动脉压（MAP）。通过RSNA和MAP对右侧附睾白色脂肪组织（eWAT）传入神经电刺激的反应来评估AAR。电刺激eWAT传入神经可增加RSNA。双侧微量注射GABAA受体激动剂异鹅膏蕈氨酸或GABAB受体激动剂巴氯芬可减弱AAR。异鹅膏蕈氨酸对AAR的作用大于巴氯芬。GABAA受体拮抗剂加巴嗪增强了AAR，而GABAB受体拮抗剂CGP-35348对AAR无显著影响。双侧PVN微量注射维加巴胺（一种选择性GABA转氨酶抑制剂）以增加PVN中的内源性GABA水平可消除AAR。加巴嗪或CGP-35348预处理可减弱维加巴胺对AAR的抑制作用。加巴嗪和CGP-35348联合预处理可消除维加巴胺的作用。
PVN中GABAA或GABAB受体的激活抑制AAR。PVN中GABAA受体的阻断增强AAR。PVN中的内源性GABA在调节AAR中起重要作用。
