Abstract P386: The Paraventricular Nucleus in Control of Blood Pressure and Its Role in Hypertension

Rationale and objectives: In 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 and both the rostral ventrolateral medulla (RVLM) and nucleus of the tractus solitarius (nTS) in the brainstem are currently viewed as key hubs for BP control and are implicated in producing or relaying the increased sympathetic tone in hypertension. We propose increased activity in the PVN, potentially through an upregulation of the renin angiotensin system, causes an increase in blood pressure. We test this theory by examining how stimulation or lesioning of the excitatory PVN neurons in conscious mice affects blood pressure and sympathetic activity. Methods: PVN and nearby glutamatergic neurons were unilaterally transduced with channelrhodopsin using an adeno-associated virus (CamKII-ChR2-eYFP-AAV) in wildtype mice. We then measured the effect of acute stimulation of excitatory PVN neurons on resting blood pressure (telemetry) and baroreflex in conscious mice. Additionally, in vGlut-cre mice glutamatergic neurons of the PVN were bilaterally lesioned utilizing a cre-dependent caspase (Dio-Caspase-AAV). We then recorded baseline resting blood pressure and baroreflex in conscious mice before and after DOCA-Salt hypertension. Finally, we measured nor-epinephrine levels as a quantification of sympathetic activity. Results and conclusions: Unilateral PVN excitation increased blood pressure from baseline by ~10 mmHg. Glutamatergic lesions of the PVN resulted in a blunted rise in BP when animals went through the DOCA-Salt protocol. These experiments demonstrate that the autonomic dysfunction seen in hypertension could be due to changes in the PVN. Overactivation of the PVN in hypertension is probably one of multiple factors that increase sympathetic drive resulting in an increased blood pressure.