The sympathetic nervous system (SNS) plays a crucial role in control of many physiological systems, including metabolism and the cardiovascular system. It is often deregulated in disease states, for example chronic heart failure is associated with increased SNS activity. We are investigating changes in SNS control of the cardiovascular system in a hypermetabolic mouse model, the Gnasxl knock-out (1). Gnasxl encodes the signalling protein XLαs, which activates cAMP signalling pathways (2). It is expressed in brain regions crucial for SNS control, including the paraventricular and dorsomedial nuclei of the hypothalamus, the nucleus of the solitary tract and the Raphe Pallidus (3). Here we show, using heart rate variability analysis, that mice lacking XLαs have increased sympathetic stimulation of the cardiovascular system. We used radio telemetry to record ECG in conscious freely-moving adult knock-out (KO) mice and wild-type (WT) siblings. Telemetric transmitters were implanted subcutaneously under isoflurane anaesthesia; following recovery ECG was recorded continuously at 5kHz. After assigning beats using a custom program, heart rate power spectra were produced using Fast Fourier Transform of 3-minute sections of clean and stable heart rate data, using Welch’s periodogram with 32-second windows and 50% overlap. Low frequency (LF) and high frequency (HF) bandings were determined empirically following inhibition of sympathetic and parasympathetic activity using reserpine and atropine, respectively. LF and HF bandings were assigned as 0.15-1.0 Hz and 1.0-5.0 Hz, respectively and validated by LF, HF and LF/HF responses to reserpine and atropine; LF/HF ratio was used as an indicator of SNS activity. Analysis of circadian heart rate and activity showed the most active period to be between 20:00 and 01:00; analysing heart rate variability during this time period showed elevated LF/HF ratio in KO compared to WT (1.73±0.20 vs 1.17±0.15, p<0.05 by t-test). Following SNS inhibition by reserpine, KO had a more substantial drop in LF/HF (1.39±0.26 to 0.26±0.06, p<0.001) than WT (1.25±0.26 to 0.47±0.09, p<0.05). Mild stress, caused by handling and scruffing of animals, elicited an increase in LF/HF in WT (1.23±0.13 to 1.86±0.20, p<0.05 by t-test), but no increase was seen in KO (1.77±0.44 to 1.66±0.44). Together, these results confirm previous data from the lab indicating that Gnasxl knock-outs have increased SNS stimulation of the cardiovascular system, and that the knock-outs may be chronically stressed. This indicates a global increase in SNS activity, and that XLαs must act centrally to inhibit SNS activity. The pathways involved will be investigated in future experiments, through targeted intracranial injections and brain slice electrophysiology.