Li De-Pei, Pan Hui-Lin
Department of Critical Care, University of Texas MD Anderson Cancer Center, Houston 77030-4009, USA.
Hypertension. 2007 Apr;49(4):916-25. doi: 10.1161/01.HYP.0000259666.99449.74. Epub 2007 Feb 19.
The paraventricular nucleus (PVN) of the hypothalamus is critical to the regulation of sympathetic output. The PVN hyperactivity is known to cause increased sympathetic nerve activity in spontaneously hypertensive rats (SHRs). The purpose of this study was to determine whether glutamatergic input to the PVN contributes to heightened sympathetic outflow in hypertension. Lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate were recorded from anesthetized SHRs and Wistar-Kyoto (WKY) rats. Bilateral microinjection of an N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonopentanoic acid, or a non-N-methyl-D-aspartate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, into the PVN dose-dependently decreased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in SHRs but not in WKY rats. Bilateral microinjection of kynurenic acid into the PVN also significantly decreased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in SHRs but not in WKY rats. Furthermore, microinjection of gabazine, a specific GABA(A) receptor antagonist, into the PVN increased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in both SHRs and WKY rats. Notably, this response was significantly attenuated in SHRs compared with that in WKY rats. In addition, kynurenic acid abolished the sympathoexcitatory and pressor responses to microinjection of gabazine into the PVN in both SHRs and WKY rats. Thus, this study provides new functional evidence that resting sympathetic vasomotor tone is maintained by tonic glutamatergic input in the PVN in SHRs. Removal of GABAergic inhibition results in augmented glutamatergic input in the PVN, which probably constitutes an important source of excitatory drive to the brain stem vasomotor neurons in hypertension.
下丘脑室旁核（PVN）对交感神经输出的调节至关重要。已知PVN功能亢进会导致自发性高血压大鼠（SHR）的交感神经活动增加。本研究的目的是确定PVN的谷氨酸能输入是否导致高血压时交感神经输出增加。记录麻醉的SHR和Wistar-Kyoto（WKY）大鼠的腰交感神经活动、平均动脉血压和心率。向PVN双侧微量注射N-甲基-D-天冬氨酸受体拮抗剂2-氨基-5-膦酰基戊酸或非N-甲基-D-天冬氨酸受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮，可剂量依赖性降低SHR的腰交感神经活动、平均动脉血压和心率，但对WKY大鼠无此作用。向PVN双侧微量注射犬尿喹啉酸也可显著降低SHR的腰交感神经活动、平均动脉血压和心率，但对WKY大鼠无此作用。此外，向PVN微量注射特异性GABA(A)受体拮抗剂加巴嗪，可增加SHR和WKY大鼠的腰交感神经活动、平均动脉血压和心率。值得注意的是，与WKY大鼠相比，SHR的这种反应明显减弱。此外，犬尿喹啉酸消除了SHR和WKY大鼠对向PVN微量注射加巴嗪的交感兴奋和升压反应。因此，本研究提供了新的功能证据，即SHR的PVN中持续性谷氨酸能输入维持了静息交感血管运动张力。去除GABA能抑制会导致PVN中谷氨酸能输入增加，这可能是高血压时脑干血管运动神经元兴奋性驱动的重要来源。
