We report dysfunction of the ANS in BACHD mice, as measured by the baroreceptor reflex. Furthermore, baseline measurements of BP and HR were higher in BACHD mice compared to WT controls. Lastly, we find changes in the morphometry of the heart, but echocardiography did not detect any functional changes at 12 mo of age.
The increased baseline BP levels measured in lightly anesthetized BACHD mice indicate changes in the overall regulation of BP tone. Importantly, these BP recordings were taken during the day, a time in the resting period of mice when BP is expected to be low. These increased BP levels parallel the reported increase in HR of BACHD mice also measured during the day 
, suggesting a global dysregulation of the cardiovascular system causing it to be hyperactive during the rest period. The blunted depression in BP levels during rest would be similar to a nondipping pressure profile observed in humans, which in many cases is an indication of dysautonomia ,
. Nondippers have a higher risk for future cardiovascular events, as well as damage to other organs ,
. Published reports of BP in Huntington’s disease patients do not detect significant differences compared to control groups, however BP measurements were taken during the day when patients are in a more active state, which could mask the higher levels of BP tone ,
. This appears to be the case for HR in BACHD mice, as HR levels are not significantly different between WT and BACHD mice during the active period 
. Therefore, it may be valuable to examine nighttime BP and HR in Huntington’s disease patients, as well as pursue circadian studies of BP in awake and freely moving BACHD mice, which would further explore the extent of dysregulation in BP. It is important to note that the BWs of BACHD mice are significantly increased at 7 mo of age compared to WT mice, possibly due to hypoactivity,
, which may contribute to the observed increase in BP in BACHD mice. This increased BW is transient, as the BWs are no longer significantly different at 12 mo of age. Comparisons of BP at this older age may indicate whether heavier BW and/or other mechanisms of BP regulation are factors involved in the increase of BP observed in BACHD mice.
The BACHD mice showed deficits in the baroreceptor reflex, whereby the response in HR to the transient hyper- and hypotension induced by ATII and NP, respectively, is blunted compared to WTs. This blunted response in both directions of the reflex suggests that both branches of the ANS may be affected. The primary deficit in the baroreceptor reflex in BACHD mice is unknown, as this process is mediated by various regions of the brain that include the brainstem and hypothalamus, along with possible deficits in the outputs from the central autonomic nervous system ,,
deposits are found globally in BACHD mice, which could disrupt function among cells in the baroreceptor pathway, even without evidence for gross degeneration of these brain regions 
. In HD patients, the detection of alterations in the baroreceptor pathway, such as the vagal nuclei and cerebral cortex, are establishing structural cause for the dysfunction ,,,,
. Ideally, identification of the site of dysfunction could be used to devise an appropriate therapeutic approach to manage symptomatic HD patients 
. In humans, similar studies have been conducted to test the response of the baroreceptor reflex. Results have been mixed, however recent studies report deficits during the Valsalva maneuver, hand-grip test, and the head up tilt test ,,,
. Furthermore, patients complain of dizziness and light-headedness upon standing, which are symptoms of baroreceptor dysregulation resulting in orthostatic hypotension ,
. Other measurements such as Heart Rate Variability and sympathetic skin response suggest that both branches of the ANS are disrupted in HD patients ,,
. During the very early stages of HD, the sympathetic nervous system appears to be hyperactive ,,
. As the disease advances, parasympathetic activity progressively decreases ,,
. In our experiments, the blunted increase in HR after NP administration in BACHD mice may be a result of a ceiling effect for sympathetic activity, in that the range for further activation is limited due to an already hyperactive sympathetic nervous system. The blunted decrease in HR after ATII administration may be a result of the dysfunction of both branches of the autonomic nervous system. The hyperactivity of the sympathetic nervous system may not allow the HR to fully depress and in addition, the progressive dysfunction of the parasympathetic nervous system may be inadequate to slow HR. Tests to measure both the sympathetic and parasympathetic nervous system activity in BACHD mice would be able to determine the extent of the dysfunction of each of the branches.
There is a high prevalence of autonomic dysfunction in Huntington’s disease patients that manifest as various clinical symptoms and signs such as gastrointestinal complaints, urinary difficulties and postural dizziness 
. More profound may be the increased risk of cardiac arrhythmias, and the development of coronary heart disease, that result in a significant number of deaths within the Huntington’s disease population ,,,
. Importantly, these autonomic symptoms occur before any motor deficits, therefore measures of autonomic dysfunction could be a valuable tool in Huntington’s disease diagnosis and staging ,
. Upon diagnosis, vigilant monitoring of the cardiovascular system may help deter the incidence of fatal events. We were able to measure changes in the morphometry of the heart in BACHD mice relative to body frame size (TL), which could indicate the start of cardiac remodeling in response to the increased BP and aberrant autonomic signaling. Echocardiogram results do not show functional changes in the hearts of BACHD mice, suggesting that the hearts at this stage of the disease are still able to compensate despite the morphological and physiological changes in the cardiovascular system. The R6/2 Huntington disease mouse model, which display a more rapid disease progression, develop serious cardiac dysfunction suggesting a cardiotoxic effect of htt
deposits in the heart 
, and we speculate that BACHD mice may develop cardiac dysfunction at an older age. Future work can be directed to study the susceptibility of this BACHD model to cardiovascular stresses as well as design management strategies focused on cardiovascular health to offset and reduce the chances of serious cardiovascular events in HD patients.