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Annual Review of Biochemistry Jun 2021Mechanosensation is the ability to detect dynamic mechanical stimuli (e.g., pressure, stretch, and shear stress) and is essential for a wide variety of processes,... (Review)
Review
Mechanosensation is the ability to detect dynamic mechanical stimuli (e.g., pressure, stretch, and shear stress) and is essential for a wide variety of processes, including our sense of touch on the skin. How touch is detected and transduced at the molecular level has proved to be one of the great mysteries of sensory biology. A major breakthrough occurred in 2010 with the discovery of a family of mechanically gated ion channels that were coined PIEZOs. The last 10 years of investigation have provided a wealth of information about the functional roles and mechanisms of these molecules. Here we focus on PIEZO2, one of the two PIEZO proteins found in humans and other mammals. We review how work at the molecular, cellular, and systems levels over the past decade has transformed our understanding of touch and led to unexpected insights into other types of mechanosensation beyond the skin.
Topics: Animals; Baroreflex; Drug Discovery; Humans; Ion Channels; Mechanotransduction, Cellular; Mice; Proprioception; Stem Cells; Touch
PubMed: 34153212
DOI: 10.1146/annurev-biochem-081720-023244 -
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 -
Journal of the American College of... Jul 2020This study demonstrated the safety and effectiveness of baroreflex activation therapy (BAT) in patients with heart failure with reduced ejection fraction (HFrEF). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This study demonstrated the safety and effectiveness of baroreflex activation therapy (BAT) in patients with heart failure with reduced ejection fraction (HFrEF).
OBJECTIVES
The BeAT-HF (Baroreflex Activation Therapy for Heart Failure) trial was a multicenter, prospective, randomized, controlled trial; subjects were randomized 1:1 to receive either BAT plus optimal medical management (BAT group) or optimal medical management alone (control group).
METHODS
Four patient cohorts were created from 408 randomized patients with HFrEF using the following enrollment criteria: current New York Heart Association (NYHA) functional class III or functional class II (patients who had a recent history of NYHA functional class III); ejection fraction ≤35%; stable medical management for ≥4 weeks; and no Class I indication for cardiac resynchronization therapy. Effectiveness endpoints were the change from baseline to 6 months in 6-min hall walk distance (6MHW), Minnesota Living with HF Questionnaire quality-of-life (QOL) score, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. The safety endpoint included the major adverse neurological or cardiovascular system or procedure-related event rate (MANCE).
RESULTS
Results from, timeline and rationale for, cohorts A, B, and C are presented in detail in the text. Cohort D, which represented the intended use population that reflected the U.S. Food and Drug Administration-approved instructions for use (enrollment criteria plus NT-proBNP <1,600 pg/ml), consisted of 245 patients followed-up for 6 months (120 in the BAT group and 125 in the control group). BAT was safe and significantly improved QOL, 6MHW, and NT-proBNP. In the BAT group versus the control group, QOL score decreased (Δ = -14.1; 95% confidence interval [CI]: -19 to -9; p < 0.001), 6MHW distance increased (Δ = 60 m; 95% CI: 40 to 80 m; p < 0.001), NT-proBNP decreased (Δ = -25%; 95% CI: -38% to -9%; p = 0.004), and the MANCE free rate was 97% (95% CI: 93% to 100%; p < 0.001).
CONCLUSIONS
BAT was safe and significantly improved QOL, exercise capacity, and NT-proBNP. (Baroreflex Activation Therapy for Heart Failure [BeAT-HF]; NCT02627196).
Topics: Aged; Baroreflex; Electric Stimulation Therapy; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Prospective Studies; Quality of Life; Stroke Volume; Ventricular Function, Left
PubMed: 32616150
DOI: 10.1016/j.jacc.2020.05.015 -
Hypertension (Dallas, Tex. : 1979) Jan 2022
Topics: Baroreflex; Blood Pressure; Pressoreceptors
PubMed: 34878899
DOI: 10.1161/HYPERTENSIONAHA.121.18372 -
Arquivos Brasileiros de Cardiologia Aug 2021
Topics: Baroreflex; Flavanones; Humans; Reperfusion Injury; Trimetazidine
PubMed: 34495222
DOI: 10.36660/abc.20210453 -
Hypertension (Dallas, Tex. : 1979) May 2023
Topics: Humans; Baroreflex; COVID-19; Pressoreceptors; Sympathetic Nervous System; Blood Pressure; Afferent Pathways
PubMed: 36802914
DOI: 10.1161/HYPERTENSIONAHA.123.20316 -
Current Hypertension Reports May 2018Most hypertension devices have been designed to interrupt or modify the sympathetic nervous system, which seems to be unbalanced in hypertension. Carotid baroreceptors... (Review)
Review
PURPOSE OF REVIEW
Most hypertension devices have been designed to interrupt or modify the sympathetic nervous system, which seems to be unbalanced in hypertension. Carotid baroreceptors play a pivotal role in maintaining adrenergic balance via a direct feedback interface and would be an exceptional target for intervention. The purpose of this review is to define the role of the baroreceptor in hypertension, to examine device-based therapies targeting the baroreflex and to explore future promises of endovascular baroreflex amplification (EBA).
RECENT FINDINGS
In the last two decades, two therapeutic strategies targeting the carotid baroreceptor have evolved: baroreflex activation therapy (BAT) and EBA. Both therapies enhance baroreceptor activity, either directly by electrical stimulation or indirectly by changing the geometric shape of the carotid sinus and increasing pulsatile wall strain. By showing a significant, sympathetic inhibition-mediated effect on blood pressure, BAT has laid the foundation for baroreflex-targeting therapies for resistant hypertension. EBA is a less invasive therapy with promising first-in-man study results. Ongoing randomized sham-controlled trials are needed to better understand efficacy, durability, and long-term safety and define phenotypes that may most benefit from this treatment.
Topics: Baroreflex; Blood Pressure; Blood Vessel Prosthesis Implantation; Carotid Sinus; Computer Simulation; Electric Stimulation Therapy; Humans; Hypertension; Pressoreceptors; Stents; Sympathetic Nervous System
PubMed: 29744599
DOI: 10.1007/s11906-018-0840-8 -
Applied Psychophysiology and Biofeedback Dec 2022This paper reviews the published work of me along with my students and close colleagues on the topic of heart rate variability biofeedback (HRVB). It includes early... (Review)
Review
This paper reviews the published work of me along with my students and close colleagues on the topic of heart rate variability biofeedback (HRVB). It includes early research by Vaschillo documenting resonance characteristics of the baroreflex system that causes large oscillations in heart rate when breathing at resonance frequency, research on heart rate variability as a marker of parasympathetic stress response in asthma, and HRVB as a treatment for asthma and depression. Many questions about HRVB remain unresolved, and important questions for future research are listed.
Topics: Humans; Heart Rate; Biofeedback, Psychology; Baroreflex; Respiration; Asthma
PubMed: 35254592
DOI: 10.1007/s10484-022-09535-5 -
Hypertension (Dallas, Tex. : 1979) Apr 2021
Topics: Baroreflex; Heart Rate; Humans; Postural Orthostatic Tachycardia Syndrome; Vagus Nerve
PubMed: 33689465
DOI: 10.1161/HYPERTENSIONAHA.121.16578 -
The Journal of Physiological Sciences :... Nov 2019This brief review summarizes the current knowledge on sex differences in baroreflex function, with a major focus on studies in humans. It has been demonstrated that... (Review)
Review
This brief review summarizes the current knowledge on sex differences in baroreflex function, with a major focus on studies in humans. It has been demonstrated that healthy women have blunted cardiovagal baroreflx sensitivity during a rapid (i.e., within seconds) hypertensive stimulus, but baroreflex sensitivity is similar between the sexes during a hypotensive stimulus. Normal aging decreases cardiovagal baroreflex sensitivity and the rate of decline is similar in men and women. Cardiovagal baroreflex sensitivity is reduced in pathological conditions such as hypertension and type II diabetes, and the reduction is greater in female patients than male patients. There is no clear sex difference in sympathetic baroreflex sensitivity among young individuals, however, with women of more advanced age, sympathetic baroreflex sensitivity decreases, which appears to be associated with greater arterial stiffness compared with similarly aged men. The blunted sympathetic baroreflex sensitivity in older women may predispose them to an increased prevalence of hypertension and cardiovascular disease.
Topics: Aging; Baroreflex; Cardiovascular Diseases; Female; Humans; Male; Sex Factors; Sympathetic Nervous System
PubMed: 31721084
DOI: 10.1007/s12576-019-00727-z