Glutamate receptors in the hypothalamic paraventricular nucleus contribute to insulin-induced sympathoexcitation.
Glutamate receptors in the hypothalamic paraventricular nucleus contribute to insulin-induced sympathoexcitation.
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下丘脑室旁核中的谷氨酸受体有助于胰岛素诱导的交感兴奋。
DOI：
10.1152/jn.00764.2014
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发表时间：
2015
影响因子：
2.5
通讯作者：
Gordon,KathrynW
中科院分区：
文献类型：
--
作者：
Stocker,SeanD;Gordon,KathrynW
对胰岛素的交感兴奋反应是由弓状核（ARC）和下丘脑室旁核（PVH）中的神经元介导的。先前的研究报道，刺激ARC神经元通过激活PVH中的谷氨酸受体增加交感神经活动（SNA）和动脉血压（ABP）。因此，本研究的目的是确定PVH中的谷氨酸能神经传递是否有助于胰岛素诱导的交感神经兴奋。雄性Sprague-Dawley大鼠（275 ~ 400 g）输注等渗生理盐水或胰岛素（3.75 mU·kg−1·min−1）加50%葡萄糖维持正常血糖。静脉输注胰岛素显著增加腰椎SNA，而平均ABP、肾SNA、心率或血糖没有显著变化。双侧PVH注射兴奋性氨基酸拮抗剂犬尿酸（KYN）降低注射胰岛素动物腰椎SNA和ABP。同样，NMDA拮抗剂-2-氨基-5-磷酸戊酸（AP5）和非NMDA拮抗剂- 6-氰-7-硝基喹啉-2,3-二酮（CNQX）的混合物在输注胰岛素时降低腰椎SNA和平均ABP。在最后的实验中，双侧PVH仅注射AP5，而不注射CNQX，可降低注射胰岛素动物的腰椎SNA和平均ABP。在KYN、AP5 + CNQX和单独使用AP5治疗的动物中，腰椎SNA和平均ABP的峰值变化无显著差异。这些药物治疗没有改变注入生理盐水的动物的任何变量。总之，这些发现表明PVH中的谷氨酸能NMDA神经传递有助于胰岛素诱导的交感神经兴奋。
The sympathoexcitatory response to insulin is mediated by neurons in the arcuate nucleus (ARC) and hypothalamic paraventricular nucleus (PVH). Previous studies have reported that stimulation of ARC neurons increases sympathetic nerve activity (SNA) and arterial blood pressure (ABP) through glutamate receptor activation in the PVH. Therefore, the purpose of the present study was to determine whether glutamatergic neurotransmission in the PVH contributes to insulin-induced sympathoexcitation. Male Sprague-Dawley rats (275–400 g) were infused with isotonic saline or insulin (3.75 mU·kg−1·min−1) plus 50% dextrose to maintain euglycemia. Intravenous infusion of insulin significantly increased lumbar SNA without a significant change in mean ABP, renal SNA, heart rate, or blood glucose. Bilateral PVH injection of the excitatory amino acid antagonist kynurenic acid (KYN) lowered lumbar SNA and ABP of animals infused with insulin. Similarly, a cocktail of the NMDA antagonistdl-2-amino-5-phosphonopentanoic acid (AP5) and non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced lumbar SNA and mean ABP during infusion of insulin. In a final experiment, bilateral PVH injection of AP5 only, but not CNQX, lowered lumbar SNA and mean ABP of animals infused with insulin. The peak changes in lumbar SNA and mean ABP of insulin-treated animals were not different between KYN, AP5 plus CNQX, or AP5 alone. These drug treatments did not alter any variable in animals infused with saline. Altogether, these findings suggest that glutamatergic NMDA neurotransmission in the PVH contributes to insulin-induced sympathoexcitation.