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Journal of Lipid Research Jul 2019The sympathetic nervous system (SNS) regulates the functions of white adipose tissue (WAT) and brown adipose tissue (BAT) tightly. Carotid baroreceptor stimulation (CBS)...
The sympathetic nervous system (SNS) regulates the functions of white adipose tissue (WAT) and brown adipose tissue (BAT) tightly. Carotid baroreceptor stimulation (CBS) efficiently inhibits SNS activation. We hypothesized that CBS would protect against obesity. We administered CBS to obese rats and measured sympathetic and AMP-activated protein kinase (AMPK)/ PPAR pathway responses as well as changes in perirenal WAT (PWAT), epididymal WAT (EWAT), and interscapular BAT (IBAT). CBS alleviated obesity-related metabolic changes, improving insulin resistance; reducing adipocyte hypertrophy, body weight, and adipose tissue weights; and decreasing norepinephrine but increasing acetylcholine in plasma, PWAT, EWAT, and IBAT. CBS also downregulated fatty acid translocase (CD36), fatty acid transport protein (FATP), phosphorylated and total hormone sensitive lipase, phosphorylated and total protein kinase A, and PPARγ in obese rats. Simultaneously, CBS upregulated phosphorylated adipose triglyceride lipase, phosphorylated and total AMPK, and PPARα in PWAT, EWAT, and IBAT. However, BAT and WAT responses differed; although many responses were more sensitive in IBAT, responses of CD36, FATP, and PPARγ were more sensitive in PWAT and EWAT. Overall, CBS decreased chronically activated SNS and ameliorated obesity-related metabolic disorders by regulating the AMPK/PPARα/γ pathway.
Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Carotid Sinus; Electric Stimulation Therapy; Glucose Tolerance Test; Male; Obesity; Pressoreceptors; Rats; Rats, Sprague-Dawley; Sympathetic Nervous System
PubMed: 31126973
DOI: 10.1194/jlr.M091256 -
Reviews in Cardiovascular Medicine Sep 2018The search of alternative methods for improving clinical management and outcomes of individuals affected by resistant hypertension has become a true health priority. In... (Review)
Review
The search of alternative methods for improving clinical management and outcomes of individuals affected by resistant hypertension has become a true health priority. In this review, we aimed at providing a timely overview and evidence synthesis on baroreflex activation therapy (BAT) and endovascular baroreflex amplification (EBA), two device-based therapies which rely on the principle of lowering blood pressure by stimulating the carotid baroreflex to decrease the sympathetic and enhance the parasympathetic activity. In resistant forms of arterial hypertension, accruing evidence has confirmed the capacity of these techniques to improve blood pressure control and to reduce the amount of anti-hypertensive therapy at cost of few side effects. Future results from ongoing randomized sham-controlled trials are eagerly awaited to best define the efficacy, safety and durability of effects in the long term before such an invasive approach may be considered as a suitable option in daily clinical practice.
Topics: Animals; Antihypertensive Agents; Baroreflex; Blood Pressure; Drug Resistance; Electric Stimulation Therapy; Humans; Hypertension; Implantable Neurostimulators; Pressoreceptors; Treatment Outcome
PubMed: 31054557
DOI: 10.31083/j.rcm.2018.03.3185 -
Journal of the American Society of... Jun 2019
Review
Topics: Animals; Humans; Ion Channels; Mechanotransduction, Cellular; Mice; Pressoreceptors; Sensitivity and Specificity
PubMed: 31043433
DOI: 10.1681/ASN.2019020160 -
Indian Journal of Pharmacology 2019The objective of the study is to develop an automatic drug infusion control system during cardiovascular surgery.
OBJECTIVES
The objective of the study is to develop an automatic drug infusion control system during cardiovascular surgery.
MATERIALS AND METHODS
Based on the clinical drug dosage analysis, the modeling of cardiovascular system with baroreceptor model is mathematically modeled using compartmental approach, considering the relationship between the volume and flow rate of blood during each heartbeat. This model is then combined with drug modeling of noradrenaline and nitroglycerine by deriving the volume and drug mass concentration equations, based on pharmacokinetics and pharmacodynamics of the drugs. The closed-loop patient models are derived from the open-loop data obtained from the physiology-drug model with covariate as age. The proportional-integral controller is designed based on optimal values obtained from bacterial foraging-oriented particle swarm optimization algorithm. The controllers are implemented individually for each control variable such as aortic pressure and cardiac output (CO), irrespective of varying weights based on the relative gain array analysis which depicts the maximum influence of cardiac drugs on control variables.
RESULTS
The physiology-drug model output responses are simulated using MATLAB. The controlled responses of aortic pressure and CO with infusion rate of cardiac drugs are obtained. The robustness of the controller is checked by introducing variations in cardiovascular model parameters. The efficiency of the controller during normal and abnormal conditions is compared using time domain analysis.
CONCLUSIONS
The controller design was efficient and can be further improved by designing switching-based controllers.
Topics: Arterial Pressure; Cardiac Output; Cardiovascular Agents; Humans; Infusions, Intravenous; Models, Cardiovascular; Nitroglycerin; Norepinephrine; Pressoreceptors
PubMed: 31031469
DOI: 10.4103/ijp.IJP_612_18 -
American Journal of Physiology. Heart... Feb 2019
Topics: Humans; Muscles; Pressoreceptors; Pulmonary Artery; Sympathetic Nervous System
PubMed: 30715905
DOI: 10.1152/ajpheart.00817.2018 -
American Journal of Physiology. Heart... Mar 2019Although redox processes closely interplay with mechanoresponses to control vascular remodeling, redox pathways coupling mechanostimulation to cellular cytoskeletal...
Although redox processes closely interplay with mechanoresponses to control vascular remodeling, redox pathways coupling mechanostimulation to cellular cytoskeletal organization remain unclear. The peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) supports postinjury vessel remodeling. Using distinct models, we investigated whether pecPDIA1 could work as a redox-dependent organizer of cytoskeletal mechanoresponses. In vascular smooth muscle cells (VSMCs), pecPDIA1 immunoneutralization impaired stress fiber assembly in response to equibiaxial stretch and, under uniaxial stretch, significantly perturbed cell repositioning perpendicularly to stretch orientation. During cyclic stretch, pecPDIA1 supported thiol oxidation of the known mechanosensor β-integrin and promoted polarized compartmentalization of sulfenylated proteins. Using traction force microscopy, we showed that pecPDIA1 organizes intracellular force distribution. The net contractile moment ratio of platelet-derived growth factor-exposed to basal VSMCs decreased from 0.90 ± 0.09 (IgG-exposed controls) to 0.70 ± 0.08 after pecPDI neutralization ( P < 0.05), together with an enhanced coefficient of variation for distribution of force modules, suggesting increased noise. Moreover, in a single cell model, pecPDIA1 neutralization impaired migration persistence without affecting total distance or velocity, whereas siRNA-mediated total PDIA1 silencing disabled all such variables of VSMC migration. Neither expression nor total activity of the master mechanotransmitter/regulator RhoA was affected by pecPDIA1 neutralization. However, cyclic stretch-induced focal distribution of membrane-bound RhoA was disrupted by pecPDI inhibition, which promoted a nonpolarized pattern of RhoA/caveolin-3 cluster colocalization. Accordingly, FRET biosensors showed that pecPDIA1 supports localized RhoA activity at cell protrusions versus perinuclear regions. Thus, pecPDI acts as a thiol redox-dependent organizer and noise reducer mechanism of cytoskeletal repositioning, oxidant generation, and localized RhoA activation during a variety of VSMC mechanoresponses. NEW & NOTEWORTHY Effects of a peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) during mechanoregulation in vascular smooth muscle cells (VSMCs) were highlighted using approaches such as equibiaxial and uniaxial stretch, random single cell migration, and traction force microscopy. pecPDIA1 regulates organization of the cytoskeleton and minimizes the noise of cell alignment, migration directionality, and persistence. pecPDIA1 mechanisms involve redox control of β-integrin and localized RhoA activation. pecPDIA1 acts as a novel organizer of mechanoadaptation responses in VSMCs.
Topics: Actin Cytoskeleton; Adaptation, Physiological; Animals; Biomechanical Phenomena; Cell Movement; Cells, Cultured; Cytoskeleton; Gene Silencing; Integrin beta1; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Oxidants; Pressoreceptors; Protein Disulfide-Isomerases; Rabbits; rhoA GTP-Binding Protein
PubMed: 30499716
DOI: 10.1152/ajpheart.00379.2018 -
Experimental Physiology Jan 2019What is the central question of this study? After sino-aortic denervation (SAD), rats present normal levels of mean arterial pressure (MAP), high MAP variability and...
NEW FINDINGS
What is the central question of this study? After sino-aortic denervation (SAD), rats present normal levels of mean arterial pressure (MAP), high MAP variability and changes in breathing. However, mechanisms involved in SAD-induced respiratory changes and their impact on the modulation of sympathetic activity remain unclear. Herein, we characterized the firing frequency of medullary respiratory neurons after SAD. What is the main finding and its importance? Sino-aortic denervation-induced prolonged inspiration was associated with a reduced interburst frequency of pre-inspiratory/inspiratory neurons and an increased long-term variability of late inspiratory neurons, but no changes were observed in the ramp-inspiratory and post-inspiratory neurons. This imbalance in the respiratory network might contribute to the modulation of sympathetic activity after SAD.
ABSTRACT
In previous studies, we documented that after sino-aortic denervation (SAD) in rats there are significant changes in the breathing pattern, but no significant changes in sympathetic activity and mean arterial pressure compared with sham-operated rats. However, the neural mechanisms involved in the respiratory changes after SAD and the extent to which they might contribute to the observed normal sympathetic activity and mean arterial pressure remain unclear. Here, we hypothesized that after SAD, rats present with changes in the firing frequency of the ventral medullary inspiratory and post-inspiratory neurons. To test this hypothesis, male Wistar rats underwent SAD or sham surgery and 3 days later were surgically prepared for an in situ experiment. The duration of inspiration significantly increased in SAD rats. During inspiration, the total firing frequency of ramp-inspiratory, pre-inspiratory/inspiratory and late-inspiratory neurons was not different between groups. During post-inspiration, the total firing frequency of post-inspiratory neurons was also not different between groups. Furthermore, the data demonstrate a reduced interburst frequency of pre-inspiratory/inspiratory neurons and an increased long-term variability of late-inspiratory neurons in SAD compared with sham-operated rats. These findings indicate that the SAD-induced prolongation of inspiration was not accompanied by alterations in the total firing frequency of the ventral medullary respiratory neurons, but it was associated with changes in the long-term variability of late-inspiratory neurons. We suggest that the timing imbalance in the respiratory network in SAD rats might contribute to the modulation of presympathetic neurons after removal of baroreceptor afferents.
Topics: Animals; Aorta; Arterial Pressure; Hypertension; Male; Neurons; Pressoreceptors; Rats, Wistar; Respiration; Sympathetic Nervous System
PubMed: 30427561
DOI: 10.1113/EP087150 -
Anesthesiology Apr 2019Baroreceptors are mechanosensitive elements of the peripheral nervous system that maintain homeostasis by coordinating physiologic responses to external and internal... (Review)
Review
Baroreceptors are mechanosensitive elements of the peripheral nervous system that maintain homeostasis by coordinating physiologic responses to external and internal stimuli. While it is recognized that carotid and cardiopulmonary baroreceptor reflexes modulate autonomic output to mitigate excessive fluctuations in arterial blood pressure and to maintain intravascular volume, increasing evidence suggests that baroreflex pathways also project to key regions of the central nervous system that regulate somatosensory, somatomotor, and central nervous system arousal. In addition to maintaining autonomic homeostasis, baroreceptor activity modulates the perception of pain, as well as neuroimmune, neuroendocrine, and cognitive responses to physical and psychologic stressors. This review summarizes the role that baroreceptor pathways play in modulating acute and chronic pain perception. The contribution of baroreceptor function to postoperative outcomes is also presented. Finally, methods that enhance baroreceptor function, which hold promise in improving postoperative and pain management outcomes, are presented.
Topics: Animals; Baroreflex; Humans; Pain; Pain Perception; Postoperative Complications; Pressoreceptors; Treatment Outcome
PubMed: 30418212
DOI: 10.1097/ALN.0000000000002510 -
The Indian Journal of Medical Research Aug 2018Although insulin resistance (IR) is a known complication in obesity, the physiological mechanisms linking IR with cardiometabolic risks in obesity have not been well...
BACKGROUND & OBJECTIVES
Although insulin resistance (IR) is a known complication in obesity, the physiological mechanisms linking IR with cardiometabolic risks in obesity have not been well studied. This study was conducted to assess the difference in cardiovascular (CV) risk profile in IR and non-IR (NIR) conditions, and contribution of IR to cardiometabolic risks in pre-obese and obese individuals.
METHODS
Basal CV, blood pressure variability, autonomic function test and cardiometabolic parameters were recorded in pre-obese (n=86) and obese (n=77) individuals during 2012 and 2015. The association of altered cardiometabolic parameters with homeostatic model for IR (HOMA-IR) in pre-obese and obese groups and with baroreceptor sensitivity (BRS) in IR and NIR groups was calculated by appropriate statistical analysis.
RESULTS
Decreased BRS, a known CV risk and cardiometabolic parameters were significant in IR (pre-obese and obese) group compared to the NIR group. Sympathovagal imbalance in the form of increased sympathetic and decreased parasympathetic activities was observed in individuals with IR. There was no significant difference in the level of independent contribution of HOMA-IR to cardiometabolic parameters in pre-obese and obese groups. Adiponectin and inflammatory markers had an independent contribution to BRS in IR group.
INTERPRETATION & CONCLUSIONS
Findings of the present study demonstrated that the intensity of cardiometabolic derangements and CV risk were comparable between IR, pre-obese and obese individuals. Pro-inflammatory state, dyslipidaemia and hypoadiponectinaemia might contribute to CV risk in these individuals with IR. IR could possibly be the link between altered metabolic profile and increased CV risks in these individuals independent of the adiposity status.
Topics: Adult; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Dyslipidemias; Female; Humans; Insulin Resistance; Lipids; Male; Metabolic Diseases; Obesity; Pressoreceptors; Risk Factors
PubMed: 30381538
DOI: 10.4103/ijmr.IJMR_1751_16 -
Science (New York, N.Y.) Oct 2018Activation of stretch-sensitive baroreceptor neurons exerts acute control over heart rate and blood pressure. Although this homeostatic baroreflex has been described for...
Activation of stretch-sensitive baroreceptor neurons exerts acute control over heart rate and blood pressure. Although this homeostatic baroreflex has been described for more than 80 years, the molecular identity of baroreceptor mechanosensitivity remains unknown. We discovered that mechanically activated ion channels PIEZO1 and PIEZO2 are together required for baroreception. Genetic ablation of both and in the nodose and petrosal sensory ganglia of mice abolished drug-induced baroreflex and aortic depressor nerve activity. Awake, behaving animals that lack had labile hypertension and increased blood pressure variability, consistent with phenotypes in baroreceptor-denervated animals and humans with baroreflex failure. Optogenetic activation of -positive sensory afferents was sufficient to initiate baroreflex in mice. These findings suggest that PIEZO1 and PIEZO2 are the long-sought baroreceptor mechanosensors critical for acute blood pressure control.
Topics: Animals; Baroreflex; Blood Pressure; Ion Channels; Mechanotransduction, Cellular; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neurons; Nodose Ganglion; Optogenetics; Pressoreceptors
PubMed: 30361375
DOI: 10.1126/science.aau6324