Pre- and postsynaptic plasticity underlying augmented glutamatergic inputs to hypothalamic presympathetic neurons in spontaneously hypertensive rats

摘要

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.