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Psychosomatic Medicine 2018High blood pressure (BP) is associated with reduced pain sensitivity, known as BP-related hypoalgesia. The underlying neural mechanisms remain uncertain, yet arterial...
OBJECTIVE
High blood pressure (BP) is associated with reduced pain sensitivity, known as BP-related hypoalgesia. The underlying neural mechanisms remain uncertain, yet arterial baroreceptor signaling, occurring at cardiac systole, is implicated. We examined normotensives using functional neuroimaging and pain stimulation during distinct phases of the cardiac cycle to test the hypothesized neural mediation of baroreceptor-induced attenuation of pain.
METHODS
Eighteen participants (10 women; 32.7 (6.5) years) underwent BP monitoring for 1 week at home, and individual pain thresholds were determined in the laboratory. Subsequently, participants were administered unpredictable painful and nonpainful electrocutaneous shocks (stimulus type), timed to occur either at systole or at diastole (cardiac phase) in an event-related design. After each trial, participants evaluated their subjective experience.
RESULTS
Subjective pain was lower for painful stimuli administered at systole compared with diastole, F(1, 2283) = 4.82, p = 0.03. Individuals with higher baseline BP demonstrated overall lower pain perception, F(1, 2164) = 10.47, p < .0001. Within the brain, painful stimulation activated somatosensory areas, prefrontal cortex, cingulate cortex, posterior insula, amygdala, and the thalamus. Stimuli delivered during systole (concurrent with baroreceptor discharge) activated areas associated with heightened parasympathetic drive. No stimulus type by cardiac phase interaction emerged except for a small cluster located in the right parietal cortex.
CONCLUSIONS
We confirm the negative associations between BP and pain, highlighting the antinociceptive impact of baroreceptor discharge. Neural substrates associated with baroreceptor/BP-related hypoalgesia include superior parietal lobule, precentral, and lingual gyrus, regions typically involved in the cognitive aspects of pain experience.
Topics: Adult; Blood Pressure; Brain; Diastole; Electric Stimulation; Female; Humans; Magnetic Resonance Imaging; Male; Pain Perception; Pressoreceptors; Systole; Young Adult
PubMed: 29595708
DOI: 10.1097/PSY.0000000000000581 -
Experimental Physiology Jun 2018What is the central question of this study? Whether anaphylaxis affects sympathetic outflows to the brown adipose tissue (BAT) and adrenal gland and whether anaphylaxis...
NEW FINDINGS
What is the central question of this study? Whether anaphylaxis affects sympathetic outflows to the brown adipose tissue (BAT) and adrenal gland and whether anaphylaxis affects some brain areas in association with sympathetic regulation. What is the main finding and its importance? Sympathoexcitatory responses to anaphylaxis occurred regionally in the kidney and adrenal gland, but not in the thermogenesis-related BAT. Further, anaphylactic hypotension also caused increase in c-fos immunoreactivity in the hypothalamic and medullary areas. Moreover, catecholaminergic neurons of the brainstem cause adrenal sympathoexcitation in a baroreceptor-independent manner.
ABSTRACT
We previously reported that sympathetic nerve activity (SNA) to the kidney and the hindlimb increases during anaphylactic hypotension in anaesthetized rats. Based on this evidence, we examined effects of anaphylactic hypotension on SNA to the brown adipose tissue (BAT), and the adrenal gland and kidney in anaesthetized rats. We demonstrated that adrenal and renal SNA, but not BAT-SNA, were stimulated. In addition, the effects of anaphylaxis on neural activities of the hypothalamic and medullary nuclei, which are candidates for relaying efferent SNA to the peripheral organs, were investigated via immunohistochemical staining of c-fos. Anaphylaxis increased c-fos expression in the neurons of the paraventricular nucleus (PVN) of the hypothalamus and in those of the nucleus tractus solitarii (NTS) and rostral ventrolateral medulla (RVLM) of the medulla oblongata; c-fos was expressed in γ-aminobutyric acid (GABA)-ergic neurons of the NTS and in the catecholaminergic neurons of the RVLM. In addition, c-fos expression in the rostral NTS and mid NTS during anaphylaxis was reduced by sinoaortic baroreceptor denervation; however, increased c-fos expression in the caudal NTS and RVLM or adrenal sympathoexcitation were not affected by sinoaortic baroreceptor denervation. These results indicated that anaphylactic hypotension activates the hypothalamic PVN and the medullary NTS and RVLM independently of the baroreflex pathway. Further, it stimulated efferent SNA to the adrenal gland and kidney to restore blood pressure.
Topics: Adipose Tissue, Brown; Anaphylaxis; Animals; Baroreflex; Blood Pressure; Denervation; Hypotension; Kidney; Male; Neurons; Paraventricular Hypothalamic Nucleus; Pressoreceptors; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Solitary Nucleus; Sympathetic Nervous System; Thermogenesis
PubMed: 29524326
DOI: 10.1113/EP086809 -
Nutrition, Metabolism, and... May 2021Our previous study found carotid baroreceptor stimulation (CBS) reduces body weight and white adipose tissue (WAT) weight, restores abnormal secretion of adipocytokines...
BACKGROUND AND AIM
Our previous study found carotid baroreceptor stimulation (CBS) reduces body weight and white adipose tissue (WAT) weight, restores abnormal secretion of adipocytokines and inflammation factors, decreases systolic blood pressure (SBP) by inhibiting activation of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in obese rats. In this study, we explore effects of CBS on aortic remodeling in obese rats.
METHODS AND RESULTS
Rats were fed high-fat diet (HFD) for 16 weeks to induce obesity and underwent either CBS device implantation and stimulation or sham operation at 8 weeks. BP and body weight were measured weekly. RAS activity of WAT, histological, biochemical and functional profiles of aortas were detected after 16 weeks. CBS effectively decreased BP in obese rats, downregulated mRNA expression of angiotensinogen (AGT) and renin in WAT, concentrations of AGT, renin, angiotensin II (Ang II), protein levels of Ang II receptor 1 (AT1R) and Ang II receptor 2 (AT2R) in WAT were declined. CBS inhibited reactive oxygen species (ROS) generation, inflammatory response and endoplasmic reticulum (ER) stress in aortas of obese rats, restrained vascular wall thickening and vascular smooth muscle cells (VSMCs) phenotypic switching, increased nitric oxide (NO) synthesis, promoted endothelium-dependent vasodilatation by decreasing protein expression of AT1R and leptin receptor (LepR), increasing protein expression of adiponectin receptor 1 (AdipoR1) in aortic VSMCs.
CONCLUSION
CBS reduced BP and reversed aortic remodeling in obese rats, the underlying mechanism might be related to the suppressed SNS activity, restored adipocytokine secretion and restrained RAS activity of WAT.
Topics: Adipokines; Adipose Tissue, White; Animals; Aorta, Thoracic; Arterial Pressure; Disease Models, Animal; Electric Stimulation Therapy; Endothelial Cells; Implantable Neurostimulators; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Obesity; Pressoreceptors; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptors, Adiponectin; Receptors, Leptin; Renin-Angiotensin System; Vascular Remodeling; Vasodilation; Rats
PubMed: 33812737
DOI: 10.1016/j.numecd.2021.01.021 -
Respiratory Care Dec 2015Cardiovascular autonomic neuropathy is one of the factors implicated in the high morbidity and mortality rate in patients with COPD. Thus, several studies and... (Review)
Review
Cardiovascular autonomic neuropathy is one of the factors implicated in the high morbidity and mortality rate in patients with COPD. Thus, several studies and nonsystematic reviews have increasingly reported autonomic function impairment in these subjects. For a better understanding, this systematic review was performed to evaluate not only the evidence for autonomic function impairment, but also factors influencing it. The results of the studies reviewed showed a strong level of evidence to support the impairment of heart rate variability in the time domain. A similar evidence level was also found to support impairment in baroreceptor sensitivity and muscle sympathetic nerve activity. Furthermore, this review identified physical activity level, muscle function, and circadian rhythm as the major influencing factors (strong evidence) of autonomic function in subjects with COPD. However, no definite conclusion could be reached for factors such as dyspnea, anxiety, body composition, pulmonary function, age, breathing frequency, ventilatory effort, quality of life, and disease severity due to limited, conflicting, or lack of existing evidence. The results of this review highlight relevant clinical messages for clinicians and other health-care providers regarding the role autonomic function can play as an important physiological marker for prognostication and stratification. Hence, autonomic function outcomes should be identified and considered during management of patients with COPD. Moreover, this review can serve as basis for future research aimed at assessing the interventions for autonomic function abnormalities in these patients.
Topics: Autonomic Nervous System; Autonomic Nervous System Diseases; Circadian Rhythm; Heart Rate; Humans; Motor Activity; Muscles; Pressoreceptors; Pulmonary Disease, Chronic Obstructive
PubMed: 26487747
DOI: 10.4187/respcare.04174 -
Current Hypertension Reports Aug 2016Congestive heart failure is characterized by hemodynamic and non-hemodynamic abnormalities, the latter including an activation of the sympathetic influences to the heart... (Review)
Review
Congestive heart failure is characterized by hemodynamic and non-hemodynamic abnormalities, the latter including an activation of the sympathetic influences to the heart and peripheral circulation coupled with an impairment of baroreceptor control of autonomic function. Evidence has been provided that both these alterations are hallmark features of the disease with a specific relevance for the disease progression as well as for the development of life-threatening cardiac arrhythmias. In addition, a number of studies have documented in heart failure the adverse prognostic role of the sympathetic and baroreflex alterations, which both are regarded as major independent determinants of cardiovascular morbidity and mortality. This represents the pathophysiological and clinical background for the use of carotid baroreceptor activation therapy in the treatment of congestive heart failure. Promising data collected in experimental animal models of heart failure have supported the recent performance of pilot small-scale clinical studies, aimed at providing initial information in this area. The results of these studies demonstrated the clinical safety and efficacy of the intervention which has been tested in large-scale clinical studies. The present paper will critically review the background and main results of the published studies designed at defining the clinical impact of baroreflex activation therapy in congestive heart failure patients. Emphasis will be given to the strengths and limitations of such studies, which represent the background for the ongoing clinical trials testing the long-term effects of the device in heart failure patients.
Topics: Animals; Arrhythmias, Cardiac; Baroreflex; Disease Models, Animal; Dogs; Electric Stimulation Therapy; Heart; Heart Failure; Hemodynamics; Humans; Hypertension; Pressoreceptors; Randomized Controlled Trials as Topic; Survival Rate; Sympathetic Nervous System
PubMed: 27334011
DOI: 10.1007/s11906-016-0667-0 -
Life Science Alliance Mar 2023Baroreceptors are nerve endings located in the adventitia of the carotid sinus and aortic arch. They act as a mechanoelectrical transducer that can sense the tension...
Baroreceptors are nerve endings located in the adventitia of the carotid sinus and aortic arch. They act as a mechanoelectrical transducer that can sense the tension stimulation exerted on the blood vessel wall by the rise in blood pressure and transduce the mechanical force into discharge of the nerve endings. However, the molecular identity of mechanical signal transduction from the vessel wall to the baroreceptor is not clear. We discovered that exogenous integrin ligands, such as RGD, IKVAV, YIGSR, PHSRN, and KNEED, could restrain pressure-dependent discharge of the aortic nerve in a dose-dependent and reversible manner. Perfusion of RGD at the baroreceptor site in vivo can block the baroreceptor reflex. An immunohistochemistry study showed the binding of exogenous RGD to the nerve endings under the adventitia of the rat aortic arch, which may competitively block the binding of integrins to ligand motifs in extracellular matrix. These findings suggest that connection of integrins with extracellular matrix plays an important role in the mechanical coupling process between vessel walls and arterial baroreceptors.
Topics: Rats; Animals; Pressoreceptors; Mechanotransduction, Cellular; Aorta; Arteries
PubMed: 36625204
DOI: 10.26508/lsa.202201785 -
American Journal of Hypertension Feb 2023The rates of uncontrolled hypertension, along with downstream cardiovascular outcomes, has been worsening in this country. Despite the plethora of antihypertensive...
BACKGROUND
The rates of uncontrolled hypertension, along with downstream cardiovascular outcomes, has been worsening in this country. Despite the plethora of antihypertensive medications on the market, the prevalence of resistant hypertension (RH) is estimated to be 13.7%. Therefore in addition to increased clinical education and focus on lifestyle management of hypertension and medication compliance, new therapies are needed to address this rise in hypertension.
METHODS
A systematic review of the available medical literature was performed to identify emerging treatment options for RH.
RESULTS
Six different pharmacologic classes and 2 procedural interventions were identified as being appropriate for review in this paper. The pharmacologic classes to be explored are non-steroidal mineralocorticoid receptor antagonists, aminopeptidase A inhibitors, dual endothelin antagonists, aldosterone synthetase inhibitors, atrial natriuretic peptide inhibitors, and attenuators of hepatic angiotensinogen. Discussion of procedural interventions to lower blood pressure will focus on renal denervation and devices that increase carotid baroreceptor activity.
CONCLUSIONS
Promising medication and procedural interventions are being developed and studied to expand our treatment arsenal for patients with uncontrolled essential hypertension and RH.
Topics: Humans; Hypertension; Antihypertensive Agents; Blood Pressure; Kidney; Pressoreceptors
PubMed: 36201204
DOI: 10.1093/ajh/hpac111 -
Experimental Physiology Oct 2023What is the topic of this review? We review barosensory vessel mechanics and their role in blood pressure regulation across the lifespan. What advances does it... (Review)
Review
NEW FINDINGS
What is the topic of this review? We review barosensory vessel mechanics and their role in blood pressure regulation across the lifespan. What advances does it highlight? In young normotensive men, aortic unloading mechanics contribute to the resting operating point of the vascular sympathetic baroreflex; however, with advancing age, this contribution is removed. This suggests that barosensory vessel unloading mechanics are not driving the well-documented age-related increase in resting muscle sympathetic nerve activity.
ABSTRACT
An age-associated increase in arterial blood pressure is evident for apparently healthy humans. This is frequently attributed to stiffening of the central arteries and a concurrent increase in sympathetic outflow, potentially mediated by a reduced ability of the baroreceptive vessels to distend. This is supported, in part, by a reduced mechanical component of the vascular sympathetic baroreflex (i.e., a reduction in distension for a given pressure). Previous characterization of the mechanical component has assessed only carotid artery distension; however, evidence suggests that both the aortic and carotid baroreflexes are integral to blood pressure regulation. In addition, given that baroreceptors are located in the vessel wall, the change in wall tension, comprising diameter, pressure and vessel wall thickness, and the mechanics of this change might provide a better index of the baroreceptor stimulus than the previous method used to characterize the mechanical component that relies on diameter alone. This brief review summarizes the data using this new method of assessing barosensory vessel mechanics and their influence on the vascular sympathetic baroreflex across the lifespan.
Topics: Male; Humans; Baroreflex; Blood Pressure; Pressoreceptors; Carotid Arteries; Sympathetic Nervous System; Homeostasis; Heart Rate
PubMed: 37031381
DOI: 10.1113/EP089686 -
Current Vascular Pharmacology 2017An imbalance in the Autonomic Nervous System (ANS) is a central pathophysiologic mechanism in Heart Failure (HF) and has been a principal target of treatment in these... (Review)
Review
INTRODUCTION
An imbalance in the Autonomic Nervous System (ANS) is a central pathophysiologic mechanism in Heart Failure (HF) and has been a principal target of treatment in these patients. Traditional pharmacologic agents do not provide specific modulation of discrete arms of the ANS, while side effects may lead to poor tolerance. Technological advances have provided a series of invasive methods that may provide a focused effect on the ANS in selected patient groups. Renal denervation, initially targeted for patients with resistant hypertension, has given positive preliminary results in terms of heart structure and function. Baroreceptor stimulation also has ongoing research with respect to its efficacy and longer term effects in HF patients. Vagal nerve stimulation and spinal cord stimulation have limited data but represent novel treatments that target the hard to reach parasympathetic system.
CONCLUSION
The present review overviews the pathophysiologic basis, current preclinical and clinical data and future expectations of these promising treatments.
Topics: Autonomic Nervous System; Heart Failure; Humans; Pressoreceptors; Spinal Cord Stimulation; Sympathectomy; Vagus Nerve Stimulation
PubMed: 28462724
DOI: 10.2174/1570161115666170428124756 -
Basic Research in Cardiology Sep 2019Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects...
Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects of CBS on the ventricular electrophysiological properties in canines with chronic heart failure (CHF). Thirty-eight beagles were randomized into control (CON), CHF, low-level CBS (LL-CBS), and moderate-level CBS (ML-CBS) groups. The CHF model was established with 6 weeks of rapid right ventricular pacing (RVP), and concomitant LL-CBS and ML-CBS were applied in the LL-CBS and ML-CBS groups, respectively. After 6 weeks of RVP, ventricular electrophysiological parameters and left stellate ganglion (LSG) neural activity and function were measured. Autonomic neural remodelling in the LSG and left ventricle (LV) and ionic remodelling in the LV were detected. Compared with the CHF group, both LL-CBS and ML-CBS decreased spatial dispersion of action potential duration (APD), suppressed APD alternans, reduced ventricular fibrillation (VF) inducibility, and inhibited enhanced LSG neural discharge and function. Only ML-CBS significantly inhibited ventricular repolarization prolongation and increased the VF threshold. Moreover, ML-CBS inhibited the increase in growth-associated protein-43 and tyrosine hydroxylase-positive nerve fibre densities in LV, increased acetylcholinesterase protein expression in LSG, and decreased nerve growth factor protein expression in LSG and LV. Chronic RVP resulted in a remarkable reduction in protein expression encoding both potassium and L-type calcium currents; these changes were partly amended by ML-CBS and LL-CBS. In conclusion, CBS suppresses VF in CHF canines, potentially by modulating autonomic nerve and ion channels. In addition, the effects of ML-CBS on ventricular electrophysiological properties, autonomic remodelling, and ionic remodelling were superior to those of LL-CBS.
Topics: Animals; Carotid Arteries; Dogs; Electric Stimulation Therapy; Electrodes, Implanted; Ion Channels; Male; Pressoreceptors; Random Allocation; Ventricular Fibrillation
PubMed: 31502080
DOI: 10.1007/s00395-019-0750-1