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NEUROSCIENCE |
1 Departments of Critical Care
2 Anaesthesiology & Pain Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
3
Program in Neuroscience, University of Texas Graduate School of Biomedical Sciences, Houston, TX 77225, USA
Increased sympathetic outflow plays an important role in the pathogenesis of hypertension. Glutamatergic inputs in the paraventricular nucleus (PVN) of the hypothalamus maintain resting sympathetic vasomotor tone in spontaneously hypertensive rats (SHR). In this study, we determined the synaptic and cellular mechanisms of increased glutamatergic inputs to PVN presympathetic neurons in SHR. The spinally projecting PVN neurons were retrogradely labelled by fluorescent microspheres injected into the intermediolateral cell column of the spinal cord. Blockade of NMDA and non-NMDA receptors significantly decreased the firing activity of labelled PVN neurons in brain slices in SHR, but not in normotensive Wistar–Kyoto rats (WKY). The basal frequency of glutamatergic spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs, respectively) of labelled PVN neurons was significantly greater in SHR than in WKY. But the frequency of neither sEPSCs nor mEPSCs stimulated by 4-aminopyridine or capsaicin differed significantly between WKY and SHR. Furthermore, the amplitude of postsynaptic NMDA currents elicited by either electrical stimulation or puff application in labelled PVN neurons was significantly higher in SHRs than in WKY. However, the evoked AMPA current amplitude in PVN neurons was similar in WKY and SHR. This study provides new evidence of how the glutamatergic synaptic inputs to PVN presympathetic neurons are increased and how they contribute to the elevated firing activity of these neurons in SHR. The augmented glutamatergic tone in the PVN is maintained by an increase in presynaptic glutamate release and an up-regulation of postsynaptic NMDA receptor function in SHR.
(Received 12 December 2007;
accepted after revision 28 January 2008;
first published online 31 January 2008)
Corresponding author H.-L. Pan: Department of Anesthesiology and Pain Medicine, Unit 110, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. Email: huilinpan{at}mdanderson.org
This article has been cited by other articles:
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D.-P. Li, Q. Yang, H.-M. Pan, and H.-L. Pan Plasticity of pre- and postsynaptic GABAB receptor function in the paraventricular nucleus in spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H807 - H815. [Abstract] [Full Text] [PDF] |
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