Heart failure (HF) is the endstage of multiple cardiovascular diseases.Impaired autonomic regulation and sympathetic-parasympathetic imbalance are considered key factors in HF progression.Baroreflex activation therapy (BAT),a novel device-based therapy which stimulates the carotid sinuses and regulates autonomic function,has demonstrated good efficacy in treating HF and improving prognosis.This review summarized the results of the latest relevant studies to provide support for further study of BAT.
Baroreflex/physiology* ; Heart Failure/therapy* ; Humans

Chronic intermittent hypobaric hypoxia (CIHH) is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension (RVH). In this study, RVH was induced by the 2-kidney-1-clip method (2K1C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii (NTS) in anesthetized rats. Evoked excitatory postsynaptic currents (eEPSCs) and spontaneous EPSCs (sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHH-treated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and eNOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via up-regulating NOS expression in the NTS.
Animals ; Baroreflex ; physiology ; Blood Pressure ; drug effects ; Hypertension ; metabolism ; Hypoxia ; chemically induced ; Kidney ; drug effects ; metabolism ; Male ; Nitric Oxide Synthase Type I ; drug effects ; metabolism ; Rats, Sprague-Dawley ; Solitary Nucleus ; metabolism

Excessive reactive oxygen species (ROS) (such as the superoxide radical) are commonly associated with cardiac autonomic dysfunctions. Though superoxide dismutase 1 (SOD1) overexpression may protect against ROS damage to the autonomic nervous system, superoxide radical reduction may change normal physiological functions. Previously, we demonstrated that human SOD1 (hSOD1) overexpression does not change baroreflex bradycardia and tachycardia but rather increases aortic depressor nerve activity in response to arterial pressure changes in C57B6SJL-Tg (SOD1)2 Gur/J mice. Since the baroreflex arc includes afferent, central, and efferent components, the objective of this study was to determine whether hSOD1 overexpression alters the central and vagal efferent mediation of heart rate (HR) responses. Our data indicate that SOD1 overexpression decreased the HR responses to vagal efferent nerve stimulation but did not change the HR responses to aortic depressor nerve (ADN) stimulation. Along with the previous study, we suggest that SOD1 overexpression preserves normal baroreflex function but may differentially alter the functions of the ADN, vagal efferents, and central components. While SOD1 overexpression likely enhanced ADN function and the central mediation of bradycardia, it decreased vagal efferent control of HR.
Animals ; Baroreflex ; physiology ; Blood Pressure ; physiology ; Bradycardia ; metabolism ; Heart Rate ; physiology ; Humans ; Mice, Transgenic ; Superoxide Dismutase-1 ; metabolism ; Vagus Nerve ; metabolism

Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha (PPAR-α), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-α and PPAR-γ was assessed in the nodose ganglion (NG) and the nucleus of the solitary tract (NTS). Hypertension induced by drinking high fructose (HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-α and PPAR-γ were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-α, the mitochondrial uncoupling protein 2 (UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats. These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.
Afferent Pathways ; drug effects ; Animals ; Antihypertensive Agents ; pharmacology ; Baroreflex ; drug effects ; Blood Pressure ; drug effects ; Fenofibrate ; pharmacology ; Male ; Oxidative Stress ; drug effects ; PPAR gamma ; drug effects ; metabolism ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transcriptional Activation ; drug effects ; Uncoupling Protein 2 ; drug effects ; metabolism ; Up-Regulation

Clinical trials and animal experimental studies have demonstrated an association of arterial baroreflex impairment with the prognosis and mortality of cardiovascular diseases and diabetes. As a primary part of the arterial baroreflex arc, the pressure sensitivity of arterial baroreceptors is blunted and involved in arterial baroreflex dysfunction in cardiovascular diseases and diabetes. Changes in the arterial vascular walls, mechanosensitive ion channels, and voltage-gated ion channels contribute to the attenuation of arterial baroreceptor sensitivity. Some endogenous substances (such as angiotensin II and superoxide anion) can modulate these morphological and functional alterations through intracellular signaling pathways in impaired arterial baroreceptors. Arterial baroreceptors can be considered as a potential therapeutic target to improve the prognosis of patients with cardiovascular diseases and diabetes.
Animals ; Baroreflex ; physiology ; Blood Pressure ; physiology ; Cardiovascular Diseases ; metabolism ; physiopathology ; Diabetes Mellitus ; metabolism ; physiopathology ; Humans ; Ion Channels ; metabolism ; Pressoreceptors ; metabolism

OBJECTIVE: Autonomic imbalance is considered a psychopathological mechanism underlying major depressive disorder (MDD). Heart rate variability (HRV) is an index for autonomic activation. Poor sleep quality is common among patients with MDD. HRV biofeedback (BF) has been used for regulating autonomic balance among patients with physical illness and mental disorders. The purpose of present study was to examine the effects of HRV-BF on depressive symptoms, sleep quality, pre-sleep arousal, and HRV indices, in patients with MDD and insomnia. METHODS: In this case-controlled study, patients with MDD and Pittsburgh Sleep Quality Index (PSQI) score higher than 6 were recruited. The HRV-BF group received weekly 60-minute protocol for 6 weeks, and the control group who have matched the age and sex received medical care only. All participants were assessed on Beck Depression Inventory-II, Back Anxiety Inventory, PSQI, and Pre-Sleep Arousal Scale. Breathing rates and electrocardiography were also performed under resting state at pre-testing, and post-testing conditions and for the HRV-BF group, also at 1-month follow-up. RESULTS: In the HRV-BF group, symptoms of depression and anxiety, sleep quality, and pre-sleep arousal were significantly improved, and increased HRV indices, compared with the control group. Moreover, in the HRV-BF group, significantly improved symptoms of depression and anxiety, decreased breathing rates, and increased HRV indices were detected at post-testing and at 1-month follow-up, compared with pre-testing values. CONCLUSION: This study confirmed that HRV-BF is a useful psychosocial intervention for improving autonomic balance, baroreflex, and symptoms of depression and insomnia in MDD patients.
Anxiety ; Arousal ; Baroreflex ; Biofeedback, Psychology ; Case-Control Studies ; Depression ; Depressive Disorder, Major ; Electrocardiography ; Follow-Up Studies ; Heart Rate ; Heart ; Humans ; Mental Disorders ; Respiration ; Sleep Initiation and Maintenance Disorders

This study aimed to analyze the impact of sleep deprivation (SD) on cardiac, hemodynamic, and endothelial parameters and to determine whether these are sustained with increased periods of SD. The study included 60 healthy men (mean: age 31.2±6.3 years; body mass index 24.6±2.6 kg/m2). Hemodynamic parameters, parameters of myocardial contractility, spectral analysis of heart rate (HR) and blood pressure (BP) variability, and the sensitivity of arterial baroreflex function were evaluated. Biochemical tests were performed to assess L-arginine (L-Arg) and asymmetric dimethylarginine (ADMA) levels in reflection of endothelial nitric oxide synthase ability. Measurements of cardiovascular system parameters were obtained at 9 a.m. (baseline) on the first day of the study and 9 a.m. (24-h SD), 1 p.m. (28-h SD), and 5 p.m. (32-h SD) on the second day. Blood samples for evaluating biochemical parameters were obtained at baseline and after 24-h SD. ANOVA Friedman's test revealed a significant effect for time in relation to HR (χ²=26.04, df=5, p=0.000), systolic BP (χ²=35.98, df=5, p=0.000), diastolic BP (χ²=18.01, df=5, p=0.003), and mean BP (χ²=28.32, df=5, p=0.000). L-Arg and ADMA levels changed from 78.2±12.9 and 0.3±0.1 at baseline to 68.8±10.2 and 0.4±0.1 after 24-hr SD, respectively (p=0.001, p=0.004). SD in healthy men is associated with increases in BP, which appear to occur after 24 hours of SD and are maintained over increasing periods of SD. The observed hemodynamic changes may have resulted due to disordered vascular endothelial function, as reflected in alterations in L-Arg and ADMA levels.
Arginine ; Autonomic Nervous System ; Baroreflex ; Blood Pressure ; Body Mass Index ; Cardiovascular System ; Heart Rate ; Hemodynamics* ; Humans ; Male ; Multiple Endocrine Neoplasia Type 1 ; Nitric Oxide Synthase Type III ; Sleep Deprivation*

BACKGROUND: Pain on injection is a limitation with propofol use. The effect of the Valsalva maneuver on pain during propofol injection has not been studied. This maneuver reduces pain through the sinoaortic baroreceptor reflex arc and by distraction. We aimed to assess the efficacy of the Valsalva maneuver in reducing pain during propofol injection. METHODS: Eighty American Society of Anesthesiologists class I adult patients undergoing general anesthesia were enrolled and divided into two groups of 40 each. Group I (Valsalva) patients blew into a sphygmomanometer tube raising the mercury column up to 30 mmHg for 20 seconds, while Group II (Control) patients did not. Anesthesia was induced with 1% propofol immediately afterwards. Pain was assessed on a 10-point visual analog scale (VAS), where 0 represented no pain, and 10, the worst imaginable pain, and a 4-point withdrawal response score, where 0 represented no pain, and 3, the worst imaginable pain. Scores were presented as median (interquartile range). RESULTS: We analyzed the data of 70 patients. The incidence of pain was significantly lower in the Valsalva than in the control group (53% vs 78%, P = 0.029). The withdrawal response score was significantly lower in the Valsalva group (1.00 [0.00-1.00] vs 2.00 [2.00-3.00], P < 0.001). The VAS score was significantly lower in the Valsalva group (1.00 [0.00-4.00] vs 7.00 [6.25-8.00], P < 0.001). CONCLUSIONS: A prior Valsalva maneuver is effective in attenuating injection pain due to propofol; it is advantageous in being a non-pharmacological, safe, easy, and time-effective technique.
Adult ; Anesthesia ; Anesthesia, General ; Baroreflex ; Humans ; Incidence ; Propofol* ; Prospective Studies* ; Sphygmomanometers ; Valsalva Maneuver* ; Visual Analog Scale

BACKGROUND AND PURPOSE: Parkinson's disease (PD) and multiple-system atrophy of the parkinsonian type (MSA-P) are progressive neurodegenerative disorders that in addition to dysfunction of the motor system also present with features of dysautonomia, frequently manifesting as orthostatic hypotension (OH). The pathophysiology of OH has been proposed to differ between these two disorders. This study investigated the spontaneous and cardiovagal baroreflex sensitivity (BRS) in Parkinson's disease patients with orthostatic hypotension (PD(OH)) and multiple system atrophy of Parkinsonian type with orthostatic hypotension in an attempt to differentiate the two disorders. METHODS: Two methods were used for determining the BRS: a spontaneous method (spontaneous BRS) and the reflexive baroreflex gain (cardiovagal BRS) from phases II and IV of the Valsalva maneuver (VM) in PD(OH) and MSA-P(OH). RESULTS: The spontaneous BRS (5.04±0.66 ms/mm Hg vs. 4.78±0.64 ms/mm Hg, p=0.54) and the cardiovagal BRS from phase II of the VM (0.96±0.75 ms/mm Hg vs. 1.34±1.51 ms/mm Hg, p=0.76) did not differ between PD(OH) and MSA-P(OH), but the cardiovagal BRS from phase IV of the VM (0.03±0.07 ms/mm Hg vs. 2.86±2.39 ms/mm Hg, p=0.004) was significantly lower in PD(OH). CONCLUSIONS: The cardiovagal BRS from phase IV of the VM has potential for differentiating PD(OH) and MSA-P(OH), indicating a difference in the pathophysiological mechanisms underlying the autonomic dysfunction in the two disorders.
Atrophy* ; Baroreflex* ; Humans ; Hypotension, Orthostatic ; Multiple System Atrophy ; Neurodegenerative Diseases ; Parkinson Disease* ; Primary Dysautonomias ; Reflex ; Valsalva Maneuver

OBJECTIVE: Anxiety trait, anxiety and depression states have all been reported to increase risks for cardiovascular disease (CVD), possibly through altering cardiac autonomic regulation. Our aim was to investigate whether the relationship between harm avoidance (HA, an anxiety-related personality trait) and cardiac autonomic regulation is independent of anxiety and depression states in healthy adults. METHODS: We recruited 535 physically and mentally healthy volunteers. Participants completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Tri-dimensional Personality Questionnaire. Participants were divided into high or low HA groups as discriminated by the quartile value. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV). We obtained the time and frequency-domain indices of HRV including variance (total HRV), the low-frequency power (LF; 0.05-0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15-0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. RESULTS: The BDI and HA scores showed associations with HRV parameters. After adjustment for the BDI scores and other control variables, HA is still associated with reduced variance, LF and HF power. Compared with the participants with low HA, those with high HA displayed significant reductions in variance, LF and HF power and a significant increase in their LF/HF ratio. CONCLUSION: This study highlights the independent role of HA in contributing to decreased autonomic cardiac regulation in healthy adults and provides a potential underlying mechanism for anxiety trait to confer increased risk for CVD.
Adult* ; Anxiety ; Baroreflex ; Cardiovascular Diseases ; Depression ; Healthy Volunteers ; Heart Rate* ; Heart* ; Humans