Rationale and objectivesIn conscious mammals the importance of neural control over sympathetic tone in relation to cardiovascular (CV) function is well established. Neuro‐CV dysregulation leads to increased sympathetic activity and neurogenic hypertension. The paraventricular nucleus (PVN) of the hypothalamus is currently viewed as one of the key hubs for BP control and is implicated in producing or relaying the increased sympathetic tone in hypertension. We hypothesize that it is through chronic over excitation of the glutamatergic PVN neurons that this central sympathetic drive is originating. We test this theory by examining how stimulation or lesioning of the excitatory PVN neurons in conscious mice affects blood pressure and sympathetic activity.Results & ConclusionGlutamatergic PVN neurons were unilaterally transduced with channelrhodopsin2 using an adeno‐associated virus (CamKII‐ChR2‐eYFP‐AAV2) in wildtype mice (N = 7). We then measured the effect of acute stimulation of excitatory PVN neurons selectively on resting blood pressure (DSI telemetry) in conscious mice. Stimulation of the PVN glutamatergic population resulted in an immediate frequency dependent (2 Hz, 10Hz, 20Hz) increase in blood pressure from baseline by ~10 mmHg at 20 Hz stimulation (p<0.001). Additionally, in vGlut2‐cre mice glutamatergic neurons of the PVN were bilaterally lesioned utilizing a cre‐dependent caspase (Dio‐Caspase‐AAV). We then recorded resting blood pressure and urinary norepinephrine levels in conscious mice before and after DOCA‐Salt hypertension. Quantified glutamatergic lesions of the PVN (39.3%, p<0.05) resulted in a blunted rise in BP when animals went through the DOCA‐salt protocol (p<0.05 at 7 day time point, N = 8). Finally, we measured nor‐epinephrine levels as a quantification of sympathetic activity between the lesion group and widtype group and observed a significant reduction after DOCA‐salt induced hypertension in the lesioned animals (p<0.05). These experiments demonstrate that stimulation of the PVN is sufficient to cause autonomic dysfunction. Additionally, the dysautonomia observed in neurogenic hypertension is due, in part, to over activation in the PVN.Support or Funding InformationHL093178‐07, HL135635‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.