Objective: 

Sympathetic activity is controlled by several areas of the central nervous system. The most referred sympatho-excitatory regions are the Paraventricular Nucleus of the Hypothalamus (PVN) and the Rostroventrolateral Medulla (RVLM). Previous data have shown an increase of PVN output on hypertension.

The aim of this study was to depress the activity of these sympatho-excitatory regions chronically (PVN / RVLM) in order to control Blood Pressure (BP) in Spontaneously Hypertensive Rats (SHR).

Methods: 

In telemetry instrumented SHR and normotensive Wistar rats (WKY), a viral vector (mix of LV-TREtigh-Kir-cIRES-GFP 5.4x10E9 and LV-Syn-Eff-G4BS-Syn-Tetoff 6.2x10E9 in a ratio 1:4) was microinjected (0.05mL) using stereotaxic coordinates for both locations. BP and Heart Rate (HR), baro and chemoreceptor reflexes were evaluated.

Results: 

In SHR the basal values for systolic, diastolic and mean BP were 159±17mmHg, 127±14mmHg, 137±14mmHg, respectively. Microinjected SHR in RVLM (n=3) and in PVN (n=4) showed a decrease in systolic (9% p=0.038; 13% p=0.217), diastolic (12% p=0.008; 17% p=0.113) and mean BP (11% p=0.013; 15% p=0.136) between 15 to 30 days post-injection.

PVN or RVLM saline microinjection in SHR (n=5) and WKY (n=5) did not significantly changed BP, neither did viral microinjection in WKY (n=6). HR and baroreflex gain did not change significantly in any experimental group (p>0.05).

Conclusions: 

These data show for the first time that the PVN and RVLM play a role in determining the long term levels of BP in conscious rats and hence make them appropriate targets for genetic targeting to control BP.