Background: The sympathetic nervous system (SNS) is responsible for the onset, development and maintenance of neurogenic hypertension. It was shown an increased activity of central sympathoexcitatory regions such as the rostroventrolateral medulla (RVLM) in an animal model of hypertension. Changes in autonomic balance can be achieved through spectral analysis of systolic blood pressure and heart rate. Objective: Depress the activity of RVLM neurons by over-expression of an inwardly rectifying potassium channel (hKir2.1) in order to establish their relative roles in the long-term regulation of blood pressure (BP) in conscious spontaneously hypertensive rats (SHR). Methods: In telemetry instrumented SHRs (n=7), a lentiviral vector LVV-hKir2.1 (LV-TREtigh-Kir-cIRES-GFP5.4x10E9: LV-Syn-Eff-G4BS-Syn-Tetoff6.2x10E9 in a ratio 1:4) was bilaterally microinjected (0.05µL) into RVLM using stereotaxic coordinates. Sham SHRs (n=4) were bilaterally microinjected with LVV-eGFP (LV-Syn-Eff-G4BS-Syn-Tetoff6.2x10E9: LV-TREtight-GFP5.7x10E9 in a ratio 1:4) in the same region. BP and Heart Rate (HR) were continuously monitored and evaluated using radio-telemetry for 75 days. Baroreflex gain was calculated by measuring heart rate changes induced by arterial pressure variation produced by phenylephrine (25μg/ml, IV) injection. The chemoreflex activation was evaluated through variations in respiratory rate evoked by the injection of lobeline (25μg/ml, IV). These procedures were performed under anaesthesia. Heart, kidneys and vessels were collected post-mortem to evaluate, by RT-PCR, the expression of 20 key genes involved in the pathways regulating blood vessel tone. Results: Depression of RVLM neurons activity in SHRs leads to a significant decrease in of systolic (157±18 to 125±25 mmHg), diastolic (126±11 to 97±25 mmHg), mean (137±12 to 106±25 mmHg) BP and HR (306±35 to 292±29 bpm) 60 days post-injection. In sham rats no significant changes were detected in all parameters. In SHRs the LF-band decreased after the LVV-hKir2.1 microinjection (0.75±0.46 to 0.53±0.16 mmHg^2). In sham rats there was an increase in LF-band. RT-PCR showed an upper regulation of endothelin a and b receptors together with an expression trend to normality of endothelin 1 and endothelin 2 genes. Conclusion: These results show that a reduction of RVLM neurons excitability caused a sustained decrease of blood pressure in SHRs. This was probably due to a reduction in sympathetic output, as evidenced by the decrease in the LF and LF/HF bands. This action is supported by changes in endothelial function due to vascular remodeling. By identifying the role of this central area in the long-term control of BP, we expect to provide realistic targets for therapeutic interventions in hypertension.