Published Online
on February 19, 2007

A more recent version of this article appeared on April 1, 2007

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Submitted on November 2, 2006
Revised on November 23, 2006

Glutamatergic Inputs in the Hypothalamic Paraventricular Nucleus Maintain Sympathetic Vasomotor Tone in Hypertension

De-Pei Li and Hui-Lin Pan^*

From the Departments of Critical Care (D.-P.L.) and Anesthesiology and Pain Medicine (H.-L.P.), University of Texas MD Anderson Cancer Center, Houston; and the Program in Neuroscience (H.-L.P.), University of Texas Graduate School of Biomedical Sciences, Houston.

^* To whom correspondence should be addressed. E-mail: huilinpan{at}mdanderson.org.

Abstract--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.

Key words: excitatory amino acids • hypothalamus • sympathetic nervous system • synaptic transmission • autonomic nervous system • NMDA receptors

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