Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems.

Chronic treatment with acetylcholinesterase inhibitors may be a promising therapeutic strategy for treatment of cardiovascular diseases. The aim of our study was to analyze the changes in blood pressure (BP) and heart rate (HR) during 14 days of treatment with two different acetylcholinesterase inhibitors - pyridostigmine (PYR) having only peripheral effects or donepezil (DON) with both peripheral and central effects. In addition, we studied their effects on the cardiovascular response to restraint stress and on sympathovagal control of HR in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). SHR were characterized by elevated BP and increased low-frequency component of systolic BP variability (LF-SBPV), but their cardiac vagal tone and HR variability (HRV) were reduced compared with WKY. Chronic treatment with either acetylcholinesterase inhibitor decreased HR and increased HRV in both strains. PYR treatment slightly decreased BP and LF-SBPV in the dark phase of the day. Neither drug significantly altered BP response to stress, but PYR attenuated HR increase during restraint stress. Regarding sympathovagal balance, acute methylatropine administration caused a greater increase of HR in WKY than in SHR. Chronic PYR or DON treatment enhanced HRV and HR response to methylatropine (vagal tone) in WKY, whereas PYR but not DON treatment potentiated HRV and vagal tone in SHR. In conclusion, vagal tone was lower in SHR compared with WKY, but was enhanced by chronic PYR treatment in both strains. Thus, chronic peripheral, but not central, acetylcholinesterase inhibition has major effects on HR and its variability in both normotensive and hypertensive rats.

BACKGROUND: A considerable link between personality types and cardiovascular diseases (CVDs) has been seen. Autonomic responses in both type A and type B personality individuals were found to be influenced by their personality traits. The study suggests further research on cardiac autonomic functions in larger sample sizes and the use of non-invasive screening techniques like cardiovascular reflex tests to stratify participants\' risk of future illness.
OBJECTIVE: This study aimed to assess autonomic stress reactivity tests in type A and type B personalities using cardiovascular reflex tests.
METHODS: This study was conducted at the Department of Physiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi. The Hunter-Wolf Personality Questionnaire Scale was used to identify 60 adults, 30 of whom were classified to have type A personality and 30 have type B personality, from the psychiatry department. Autonomic function tests, such as the handgrip tests, cold pressor test, deep breathing test (DBT), lying-to-standing test (LST), and Valsalva maneuver, were performed and recorded for each subject. IBM SPSS Statistics for Windows, version 21 (released 2012; IBM Corp., Armonk, New York, United States) was used for the compilation and analysis of data.
RESULTS:  The E:I (expiration-to-inspiration) ratio and delta heart rate of the type A personality patients both significantly decreased (p = 0.000*) as compared to the type B personality patients (1.18 ± 0.03 versus 1.25 ± 0.77 and 1.18 ± 0.03 versus 1.25 ± 0.77). The Valsalva ratio of the type A personality patients decreased (1.38 ± 0.10) as compared to the type B personality patients (1.48 ± 0.18), which was statistically significant (p = 0.001*). The 30:15 ratio in the type A personality patients was significantly decreased (p = 0.03*) compared to the type B personality patients (1.12 ± 0.05 versus 1.15 ± 0.10). The handgrip test and cold pressor test results were statistically insignificant.
CONCLUSIONS: Compared to the type B personality patients, which exhibited an increase in both parasympathetic and sympathetic reactivity, the type A personality patients exhibited a reduction in resting cardiovascular parameters and resting autonomic tone. Consequently, in order to stratify the participants\' risk of future illness, we recommend employing non-invasive procedures, such as cardiovascular reflex tests, as a screening technique.

Dysregulation of the autonomic nervous system (ANS) is commonly observed in various mental disorders, particularly when individuals engage in prolonged cognitive-emotional tasks that require ANS adjustment to workload. Although the understanding of the temporal dynamics of sympathetic and parasympathetic tones in obsessive-compulsive disorder (OCD) is limited, analyzing ANS reactions to cognitive-emotional workload could provide valuable insights into one of the underlying causes of OCD. This study investigated the temporal dynamics of heart rate (HR) and pupil area (PA) while participants with OCD and healthy volunteers solved antisaccade tasks, with affective pictures serving as central fixation stimuli. The data of 31 individuals with OCD and 30 healthy volunteers were included in the study, comprising three separate blocks, each lasting approximately 8 min. The results revealed an increase in sympathetic tone in the OCD group, with the most noticeable rise occurring during the middle part of each block, particularly during the presentation of negative stimuli. Healthy volunteers demonstrated adaptive temporal dynamics of HR and PA from the first block to the last block of tasks, whereas individuals with OCD exhibited fewer changes over time, suggesting a reduced adaptation of the ANS sympathetic tone to cognitive-emotional workload in OCD.

Arterial stiffening contributes to hemodynamic derangements in heart failure with preserved ejection fraction (HFpEF). We sought to investigate the impact of renal denervation on pulsatile left ventricular loading in patients with HFpEF and hypertensive patients without heart failure (control).
Patients underwent renal denervation for treatment of hypertension and were followed up at 3 months at a single center. A validated computer model of the arterial tree, noninvasive aortic flow curves, left ventricular volumes, and E/e\' as inputs were used to determine key parameters of left ventricular vascular load.
In comparison to controls (n=30), patients with HFpEF (n=30) demonstrated lower total arterial compliance (mean difference, -0.41 [95% CI, -0.72 to -0.10] mL/mm Hg), higher impedance of the proximal aorta (Zc: 0.02; 0.01 to 0.04 mHg·s/mL), premature wave reflections (shorter backward wave transit time normalized to ejection time: -3.5; -6.5% to -0.5%), and higher wave reflection magnitude (reflection coefficient: 7.3; 2.8% to 11.9%). Overall, daytime systolic (-9.2; -12.2 to -6.2 mm Hg) and diastolic blood pressures (-5.9; -7.6 to -4.1 mm Hg) as well as blood pressure variability (-2.0; -3.0 to -0.9 mm Hg) decreased after renal denervation. In patients with HFpEF, total arterial compliance (0.42; 0.17 to 0.67 mL/mm Hg) and backward transit time normalized to ejection time (1.7; 0.4% to 3.0%) increased; Zc (-0.01; -0.02 to -0.01 mm Hg·s/mL) and reflection coefficient (-2.6; -5.0% to -0.3%) decreased after renal denervation. This was accompanied by a symptomatic improvement in patients with HFpEF.
HFpEF is characterized by heightened aortic stiffness and unfavorable pulsatile left ventricular load. These abnormalities are partly normalized after renal denervation.

Levels of circulating fatty acid binding protein 4 (FABP4) protein are strongly associated with obesity and metabolic disease in both mice and humans, and secretion is stimulated by β-adrenergic stimulation both in vivo and in vitro. Previously, lipolysis-induced FABP4 secretion was found to be significantly reduced upon pharmacological inhibition of adipose triglyceride lipase (ATGL) and was absent from adipose tissue explants from mice specifically lacking ATGL in their adipocytes (ATGLAdpKO). Here, we find that upon activation of β-adrenergic receptors in vivo, ATGLAdpKO mice unexpectedly exhibited significantly higher levels of circulating FABP4 as compared with ATGLfl/fl controls, despite no corresponding induction of lipolysis. We generated an additional model with adipocyte-specific deletion of both FABP4 and ATGL (ATGL/FABP4AdpKO) to evaluate the cellular source of this circulating FABP4. In these animals, there was no evidence of lipolysis-induced FABP4 secretion, indicating that the source of elevated FABP4 levels in ATGLAdpKO mice was indeed from the adipocytes. ATGLAdpKO mice exhibited significantly elevated corticosterone levels, which positively correlated with plasma FABP4 levels. Pharmacological inhibition of sympathetic signaling during lipolysis using hexamethonium or housing mice at thermoneutrality to chronically reduce sympathetic tone significantly reduced FABP4 secretion in ATGLAdpKO mice compared with controls. Therefore, activity of a key enzymatic step of lipolysis mediated by ATGL, per se, is not required for in vivo stimulation of FABP4 secretion from adipocytes, which can be induced through sympathetic signaling.

The autonomic profile of mice submitted to sustained hypoxia (SH) was not yet fully evaluated. Herein, we characterized the cardiovascular and autonomic profile of conscious freely moving mice submitted to SH using two sequential experimental protocols to evaluate the parasympathetic and sympathetic tone to the heart and the sympathetic tone to the vascular resistance. In the first protocol the sequence of antagonists was methyl-atropine followed by propranolol and then by prazosin, while in the second protocol the sequence was propranolol followed by methyl-atropine and then by prazosin. In SH the baseline heart rate was significantly lower than in control mice and the antagonism of the parasympathetic and sympathetic tone to the heart in both experimental protocols indicated an increased parasympathetic tone in SH mice and no changes in the sympathetic tone. Antagonism of the sympathetic tone to the vascular resistance with prazosin produced similar changes in arterial pressure in control and SH mice. Altogether these findings support the concept that mice submitted to SH present a significant increase in the parasympathetic but not in the sympathetic tone, which may explain why the baseline arterial pressure was not increased in SH mice.

Spectral analysis of heart rate (HR) and blood pressure (BP) variabilities (BPV and HRV) is widely available and utilized in understanding the dynamic cardiovascular autonomic regulation in a variety of pathophysiological conditions. In conscious cold-stressed (CS) rats, we examined the effect of a 7-day regimen administration of losartan, a selective nonpeptide angiotensin AT1 receptor blockade, on BPV and HRV at three frequency components: very-low frequency (VLF), low frequency (LF), and high frequency (HF). Key findings in changes of systolic BP (SBP), HR, and spectral power densities for cardiopulmonary oscillations (HF), sympathetic oscillations (LF), cardiovascular myogenic oscillations (VLF), and overall autonomic activity total power (TP) showed: (I) In the resting PreCS trial, compared with the saline, losartan increased HFBPV, TPHRV, all three HRV frequency powers, and the occurrence of the dicrotic notch (DN). However, it decreased SBP, HR, and the LFBPV frequency power. (II) In the CS trial, losartan significantly decreased SBP and DN occurrence and HR and LF/HFHRV but significantly increased HFHRV, TPBPV, and all three BPV frequency powers. In addition, similar to the saline, losartan showed positively correlated LFBPV and VLFBPV. Conversely, losartan converted the original inverse correlations between LFHRV and LFBPV of CS to a positive correlation. (III) Compared with saline in PreCS and CS trials, losartan detached the corresponding sympathetic oscillations between LFBPV and LFHRV. The overall result indicates that endogenous angiotensin II, through stimulation of the AT1 receptor, augments sympathetic tone but attenuates sympathetic oscillations in rats, particularly under the stressful cooling impacts.

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This paper reports on the multicentric validation of a novel FDA-cleared home sleep apnea test based on peripheral arterial tonometry (PAT HSAT).
One hundred sixty-seven participants suspected of having obstructive sleep apnea (OSA) were included in a multicentric cohort. All patients underwent simultaneous polysomnography (PSG) and PAT HSAT, and all PSG data were independently double scored using both the recommended 1A rule for hypopnea, requiring a 3% desaturation or arousal (3% Rule), and the acceptable 1B rule for hypopnea, requiring a 4% desaturation (4% Rule). The double-scoring of PSG enabled a comparison of the agreement between PAT HSAT and PSG to the inter-rater agreement of PSG. Clinical endpoint parameters were selected to evaluate the device\'s ability to determine the OSA severity category. Finally, a correction for near-boundary apnea-hypopnea index values was proposed to adequately handle the inter-rater variability of the PSG benchmark.
For both the 3% and the 4% Rules, most endpoint parameters showed a close agreement with PSG. The 4-way OSA severity categorization accuracy of PAT HSAT was strong, but nevertheless lower than the inter-rater agreement of PSG (70% vs 77% for the 3% Rule and 78% vs 81% for the 4% Rule).
This paper reported on a multitude of robust endpoint parameters, in particular OSA severity categorization accuracies, while also benchmarking clinical performances against double-scored PSG. This study demonstrated strong agreement of PAT HSAT with PSG. The results of this study also suggest that different brands of PAT HSAT may have distinct clinical performance characteristics.