Median preoptic nucleus and subfornical organ drive renal sympathetic nerve activity via a glutamatergic mechanism within the PVN

The activity within the paraventricular nucleus (PVN) may be dictated by input from higher forebrain areas, such as the median preoptic nucleus (MnPO) and the subfornical organ (SFO). We hypothesized that activation of the MnPO or SFO would drive the PVN via a glutamatergic pathway. Neuroanatomical connections were identified using a retrograde tracer from the PVN to the MnPO and SFO. NMDA and bicuculline (BIC) induced activation of MnPO neurons increased renal sympathetic activity (RSNA), blood pressure (BP), and heart rate (HR). These responses were attenuated by microinjection of glutamate receptor blocker (AP5) into the PVN (NMDA ‐ ΔRSNA 72.4±7.6% compared to 4.6±0.7%; p < .05). Using single‐unit extracellular recording, we examined the effect of NMDA microinjection into the MnPO on the firing activity of PVN neurons. Of the 11 active neurons in the PVN, 6 neurons were excited by 95±17% (p < .05), 1 was inhibited by 57%, and 4 did not respond. Activations of the SFO by angiotensin II (ANG II) or BIC microinjections were attenuated by blockade of the PVN with AP5 (ANG II ‐ ΔRSNA 46±6.8% compared to 17±4.1%; p < .05). Prior microinjection of ANG II type 1 receptor blocker, losartan, into the PVN didn't reduce the BIC‐induced sympathoexcitation in the SFO. The results from this study demonstrate that sympathoexcitation mediated by a glutamatergic mechanism in the PVN is partially driven by the activation of the MnPO or SFO.