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The Journal of Clinical Investigation Oct 2020Intermittent hypoxia (IH) is a hallmark manifestation of obstructive sleep apnea (OSA), a widespread disorder of breathing. This Review focuses on the role of... (Review)
Review
Intermittent hypoxia (IH) is a hallmark manifestation of obstructive sleep apnea (OSA), a widespread disorder of breathing. This Review focuses on the role of hypoxia-inducible factors (HIFs) in hypertension, type 2 diabetes (T2D), and cognitive decline in experimental models of IH patterned after O2 profiles seen in OSA. IH increases HIF-1α and decreases HIF-2α protein levels. Dysregulated HIFs increase reactive oxygen species (ROS) through HIF-1-dependent activation of pro-oxidant enzyme genes in addition to reduced transcription of antioxidant genes by HIF-2. ROS in turn activate chemoreflex and suppress baroreflex, thereby stimulating the sympathetic nervous system and causing hypertension. We also discuss how increased ROS generation by HIF-1 contributes to IH-induced insulin resistance and T2D as well as disrupted NMDA receptor signaling in the hippocampus, resulting in cognitive decline.
Topics: Animals; Baroreflex; Basic Helix-Loop-Helix Transcription Factors; Carotid Body; Cognitive Dysfunction; Diabetes Mellitus, Type 2; Disease Models, Animal; Epigenesis, Genetic; Humans; Hypertension; Hypoxia; Hypoxia-Inducible Factor 1; Insulin Resistance; Mice; Models, Biological; Rats; Reactive Oxygen Species; Signal Transduction; Sleep Apnea, Obstructive
PubMed: 32730232
DOI: 10.1172/JCI137560 -
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 -
American Journal of Physiology. Heart... Mar 2022Short sleep duration and poor sleep quality are associated with cardiovascular risk, and sympathetic nervous system (SNS) dysfunction appears to be a key contributor.... (Review)
Review
Short sleep duration and poor sleep quality are associated with cardiovascular risk, and sympathetic nervous system (SNS) dysfunction appears to be a key contributor. The present review will characterize sympathetic function across several sleep disorders and insufficiencies in humans, including sleep deprivation, insomnia, narcolepsy, and obstructive sleep apnea (OSA). We will focus on direct assessments of sympathetic activation, e.g., plasma norepinephrine and muscle sympathetic nerve activity, but include heart rate variability (HRV) when direct assessments are lacking. The review also highlights sex as a key biological variable. Experimental models of total sleep deprivation and sleep restriction are converging to support several epidemiological studies reporting an association between short sleep duration and hypertension, especially in women. A systemic increase of SNS activity via plasma norepinephrine is present with insomnia and has also been confirmed with direct, regionally specific evidence from microneurographic studies. Narcolepsy is characterized by autonomic dysfunction via both HRV and microneurographic studies but with opposing conclusions regarding SNS activation. Robust sympathoexcitation is well documented in OSA and is related to baroreflex and chemoreflex dysfunction. Treatment of OSA with continuous positive airway pressure results in sympathoinhibition. In summary, sleep disorders and insufficiencies are often characterized by sympathoexcitation and/or sympathetic/baroreflex dysfunction, with several studies suggesting women may be at heightened risk.
Topics: Animals; Humans; Norepinephrine; Sleep Wake Disorders; Sympathetic Nervous System
PubMed: 34995163
DOI: 10.1152/ajpheart.00590.2021 -
Neuron Dec 2022Sleep disturbances are strongly associated with cardiovascular diseases. Baroreflex, a basic cardiovascular regulation mechanism, is modulated by sleep-wake states....
Sleep disturbances are strongly associated with cardiovascular diseases. Baroreflex, a basic cardiovascular regulation mechanism, is modulated by sleep-wake states. Here, we show that neurons at key stages of baroreflex pathways also promote sleep. Using activity-dependent genetic labeling, we tagged neurons in the nucleus of the solitary tract (NST) activated by blood pressure elevation and confirmed their barosensitivity with optrode recording and calcium imaging. Chemogenetic or optogenetic activation of these neurons promoted non-REM sleep in addition to decreasing blood pressure and heart rate. GABAergic neurons in the caudal ventrolateral medulla (CVLM)-a downstream target of the NST for vasomotor baroreflex-also promote non-REM sleep, partly by inhibiting the sympathoexcitatory and wake-promoting adrenergic neurons in the rostral ventrolateral medulla (RVLM). Cholinergic neurons in the nucleus ambiguous-a target of the NST for cardiac baroreflex-promoted non-REM sleep as well. Thus, key components of the cardiovascular baroreflex circuit are also integral to sleep-wake brain-state regulation.
Topics: Sleep
PubMed: 36170850
DOI: 10.1016/j.neuron.2022.08.027 -
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 -
American Journal of Physiology. Heart... Jan 2021Electronic cigarettes (e-cigarettes) are marketed as an alternative to smoking for those who want to decrease the health risks of tobacco. Tobacco cigarettes increase... (Randomized Controlled Trial)
Randomized Controlled Trial
Electronic cigarettes (e-cigarettes) are marketed as an alternative to smoking for those who want to decrease the health risks of tobacco. Tobacco cigarettes increase heart rate (HR) and arterial pressure, while reducing muscle sympathetic nerve activity (MSNA) through sympathetic baroreflex inhibition. The acute effects of e-cigarettes on arterial pressure and MSNA have not been reported: our purpose was to clarify this issue. Using a randomized crossover design, participants inhaled on a JUUL e-cigarette containing nicotine (59 mg/mL) and a similar placebo e-cigarette (0 mg/mL). Experiments were separated by ∼1 mo. We recorded baseline ECG, finger arterial pressure ( = 15), and MSNA ( = 10). Subjects rested for 10 min (BASE) and then inhaled once every 30 s on an e-cigarette that contained nicotine or placebo (VAPE) for 10 min followed by a 10-min recovery (REC). Data were expressed as Δ means ± SE from BASE. Heart rate increased in the nicotine condition during VAPE and returned to BASE values in REC (5.0 ± 1.3 beats/min nicotine vs. 0.1 ± 0.8 beats/min placebo, during VAPE; < 0.01). Mean arterial pressure increased in the nicotine condition during VAPE and remained elevated during REC (6.5 ± 1.6 mmHg nicotine vs. 2.6 ± 1 mmHg placebo, during VAPE and 4.6.0 ± 1.7 mmHg nicotine vs. 1.4 ± 1.4 mmHg placebo, during REC; < 0.05). MSNA decreased from BASE to VAPE and did not restore during REC (-7.1 ± 1.6 bursts/min nicotine vs. 2.6 ± 2 bursts/min placebo, during VAPE and -5.8 ± 1.7 bursts/min nicotine vs. 0.5 ± 1.4 bursts/min placebo, during REC; < 0.05). Our results show that acute e-cigarette usage increases mean arterial pressure leading to a baroreflex-mediated inhibition of MSNA. The JUUL e-cigarette is the most popular e-cigarette in the market. In the present study, inhaling on a JUUL e-cigarette increased mean arterial pressure and heart rate, and decreased muscle sympathetic nerve activity (MSNA). In contrast, inhaling on a placebo e-cigarette without nicotine elicited no sympathomimetic effects. Although previous tobacco cigarette studies have demonstrated increased mean arterial pressure and MSNA inhibition, ours is the first study to report similar responses while inhaling on an e-cigarette. Listen to this article's corresponding podcast at @ https://ajpheart.podbean.com/e/aerosolized-nicotine-and-cardiovascular-control/.
Topics: Administration, Inhalation; Aerosols; Age Factors; Arterial Pressure; Baroreflex; Cardiovascular System; Cross-Over Studies; E-Cigarette Vapor; Electronic Nicotine Delivery Systems; Female; Heart Rate; Humans; Male; Muscle, Skeletal; Nicotine; Nicotinic Agonists; Non-Smokers; Sympathetic Nervous System; Time Factors; Vaping; Young Adult
PubMed: 33164580
DOI: 10.1152/ajpheart.00448.2020 -
Hypertension (Dallas, Tex. : 1979) Jan 2022
Topics: Baroreflex; Blood Pressure; Pressoreceptors
PubMed: 34878899
DOI: 10.1161/HYPERTENSIONAHA.121.18372 -
Neural Regeneration Research Oct 2020Variability in cardiovascular spectra was first described by Stephan Hales in 1733. Traube and Hering initially noted respirophasic variation of the arterial pressure... (Review)
Review
Variability in cardiovascular spectra was first described by Stephan Hales in 1733. Traube and Hering initially noted respirophasic variation of the arterial pressure waveform in 1865 and Sigmund Mayer noted a lower frequency oscillation of the same in anesthetized rabbits in 1876. Very low frequency oscillations were noted by Barcroft and Nisimaru in 1932, likely representing vasogenic autorhythmicity. While the origins of Traube Hering and very low frequency oscillatory variability in cardiovascular spectra are well described, genesis mechanisms and functional significance of Mayer waves remain in controversy. Various theories have posited baroreflex and central supraspinal mechanisms for genesis of Mayer waves. Several studies have demonstrated the persistence of Mayer waves following high cervical transection, indicating a spinal capacity for genesis of these oscillations. We suggest a general tendency for central sympathetic neurons to oscillate at the Mayer wave frequency, the presence of multiple Mayer wave oscillators throughout the brainstem and spinal cord, and possible contemporaneous genesis by baroreflex and vasomotor mechanisms.
PubMed: 32246623
DOI: 10.4103/1673-5374.280306 -
Arquivos Brasileiros de Cardiologia Aug 2021
Topics: Baroreflex; Flavanones; Humans; Reperfusion Injury; Trimetazidine
PubMed: 34495222
DOI: 10.36660/abc.20210453