Regulation of Hypothalamic Presympathetic Neurons and Sympathetic Outflow by Group II Metabotropic Glutamate Receptors in Spontaneously Hypertensive Rats.
Regulation of Hypothalamic Presympathetic Neurons and Sympathetic Outflow by Group II Metabotropic Glutamate Receptors in Spontaneously Hypertensive Rats.
复制标题
DOI：
10.1161/hypertensionaha.113.01466
复制
发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Pan HL
中科院分区：
文献类型：
--
作者：
Ye ZY;Li DP;Pan HL
下丘脑室旁核(PVN)谷氨酸能投入量增加在高血压的发生发展中起重要作用。第二组代谢性谷氨酸受体(MGluRs)在下丘脑室旁核表达，但其在高血压中调节突触传递和交感神经流出的作用尚不清楚。本研究表明，在自发性高血压大鼠(SHR)脊髓投射的下丘脑室旁核神经元上，II组mGluRs激动剂(2S，2‘R，3’R)-2-(2‘，3’-dicarboxycyclopropyl)glycine(DCG-IV)对自发和微小兴奋性突触后电流的频率和电诱发兴奋性突触后电流的幅度的降低明显高于正常血压对照组大鼠。DCG-IV同样降低两组大鼠标记的PVN神经元GABA能抑制性突触后电流的频率。值得注意的是，DCG-IV仅抑制SHR标记的PVN神经元的放电。在离子型谷氨酸受体拮抗剂存在下，DCG-IV不能抑制SHR下丘脑室旁核神经元的放电。在SHR中，通过腹腔神经节切除术降低血压，使DCG-IV对兴奋性突触后电流的影响正常化到与对照组大鼠相同的水平。此外，PVN内微量注射DCG-IV可显著降低SHR的血压和交感神经活动。我们的发现提供了新的信息，即SHR的PVN中突触前II组mGluR的谷氨酸能终末活性增加。激活PVN中的II组mGluRs可通过减弱SHR增加的谷氨酸能输入和神经元的过度活动来抑制交感血管舒张性张力。
Increased glutamatergic input in the hypothalamic paraventricular nucleus (PVN) plays an important role in the development of hypertension. Group II metabotropic glutamate receptors (mGluRs) are expressed in the PVN, but their involvement in regulating synaptic transmission and sympathetic outflow in hypertension is unclear. Here we show that the group II mGluRs agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) produced a significantly greater reduction in the frequency of spontaneous and miniature excitatory postsynaptic currents and the amplitude of electrically evoked excitatory postsynaptic currents in retrogradely labeled spinally projecting PVN neurons in spontaneously hypertensive rats (SHRs) than in normotensive control rats. DCG-IV similarly decreased the frequency of GABAergic inhibitory postsynaptic currents of labeled PVN neurons in the two groups of rats. Strikingly, DCG-IV suppressed the firing of labeled PVN neurons only in SHRs. DCG-IV failed to inhibit the firing of PVN neurons of SHRs in the presence of ionotropic glutamate receptor antagonists. Lowering blood pressure with celiac ganglionectomy in SHRs normalized the DCG-IV effect on excitatory postsynaptic currents to the same level seen in control rats. Furthermore, microinjection of DCG-IV into the PVN significantly reduced blood pressure and sympathetic nerve activity in SHRs. Our findings provide new information that presynaptic group II mGluR activity at the glutamatergic terminals increases in the PVN in SHRs. Activation of group II mGluRs in the PVN inhibits sympathetic vasomotor tone through attenuation of increased glutamatergic input and neuronal hyperactivity in SHRs.