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Hypertension (Dallas, Tex. : 1979) Jun 2020Nighttime blood pressure (BP) generally dips by 10% to 20% of the daytime values, and abnormal BP dipping may affect vascular health independently of BP level. The...
Nighttime blood pressure (BP) generally dips by 10% to 20% of the daytime values, and abnormal BP dipping may affect vascular health independently of BP level. The regulation of BP dipping involves arterial baroreflex, whose receptors mainly reside in carotid sinuses and aortic arch. Atherosclerosis in these baroreceptor-resident arteries (BRAs) is frequent among patients with ischemic stroke (IS) and might impair their BP-regulating capacity. We aimed to examine associations between atherosclerosis of BRA and BP dipping in patients with IS. BP dipping ratio was measured by 24-hour ambulatory blood pressure monitoring on the sixth day after IS. With computed tomography angiography, atherosclerosis conditions in 10 segments of carotid sinuses and aortic arch were scored and summed as total atherosclerosis burden of BRA. Among the 245 patients with IS, 78.0% had atherosclerosis in BRA. The total AS burden of BRA was negatively correlated with systolic BP dipping ratio (=-0.331; <0.001) and diastolic BP dipping ratio (=-0.225; <0.001). After adjusting for age, sex, vascular risk factors, 24-hour BP means, cervical and intracranial atherosclerosis scores, the negative correlations still existed (adjusted β, -0.259 [95% CI, -0.416 to -0.102] and adjusted β, -0.178 [95% CI, -0.346 to -0.010], respectively). In conclusion, higher total atherosclerosis burden of BRA was independently indicative of more blunted dipping of systolic BP and diastolic BP in IS. The total atherosclerosis burden of BRA might be important for predicting and managing BP dipping in patients with IS.
Topics: Aged; Aorta, Thoracic; Atherosclerosis; Blood Pressure Monitoring, Ambulatory; Carotid Sinus; Computed Tomography Angiography; Correlation of Data; Female; Heart Disease Risk Factors; Humans; Hypotension; Ischemic Stroke; Male; Pressoreceptors; Severity of Illness Index
PubMed: 32336234
DOI: 10.1161/HYPERTENSIONAHA.120.15036 -
Respiratory Physiology & Neurobiology Jul 2020ATP-sensitive K (K) channels contribute to exercise-induced hyperemia in skeletal muscle either locally by vascular hyperpolarization or by sympathoinhibition and...
ATP-sensitive K (K) channels contribute to exercise-induced hyperemia in skeletal muscle either locally by vascular hyperpolarization or by sympathoinhibition and decreased sympathetic vasoconstriction. However, mean arterial pressure (MAP) regulation via baroreceptors and subsequent efferent activity may confound assessment of vascular versus neural K channel function. We hypothesized that systemic K channel inhibition via glibenclamide (GLI) would increase MAP without increasing sympathetic nerve discharge (SND). Lumbar and renal nerve SND were measured in anesthetized male rats with intact baroreceptors (n = 12) and sinoaortic denervated (SAD; n = 4) counterparts and blood flow (BF) and vascular conductance (VC) assessed in conscious rats (n = 6). GLI increased MAP (p < 0.05) and transiently decreased HR in intact (p < 0.05), but not SAD rats. Renal (-30 %) and lumbar (-40 %) ΔSND decreased in intact but increased in SAD rats (∼40 % and 20 %; p < 0.05). BF and VC decreased in kidneys and total hindlimb skeletal muscle (p < 0.05). Thus, because K inhibition decreases SND, GLI-induced reductions in blood flow cannot result from enhanced sympathetic activity.
Topics: Animals; Arterial Pressure; Glyburide; KATP Channels; Muscle, Skeletal; Pressoreceptors; Rats; Regional Blood Flow; Renal Artery; Renal Circulation; Sympathetic Nervous System; Vasoconstriction
PubMed: 32330600
DOI: 10.1016/j.resp.2020.103444 -
Current Hypertension Reports Mar 2020Patients with true resistant hypertension (RH) are characterized by having high sympathetic activity and therefore potentially benefit from treatments such as baroreflex... (Review)
Review
PURPOSE OF REVIEW
Patients with true resistant hypertension (RH) are characterized by having high sympathetic activity and therefore potentially benefit from treatments such as baroreflex amplification (baroreflex activation therapy (BAT) or endovascular baroreflex amplification therapy (EVBA)) or carotid body (CB) modulation. This review aims at providing an up-to-date overview of the available evidence regarding these two therapies.
RECENT FINDINGS
In recent years, increasing evidence has confirmed the potential of baroreflex amplification, either electrically (Barostim neo) or mechanically (MobiusHD), to improve blood pressure control on short- and long-term with only few side effects, in patients with RH. Two studies regarding unilateral CB resection did not show a significant change in blood pressure. Only limited studies regarding CB modulation showed promising results for transvenous CB ablation, but not for unilateral CB resection. Despite promising results from mostly uncontrolled studies, more evidence regarding the safety and efficacy from ongoing large randomized sham-controlled trials is needed before baroreflex amplification and CB modulation can be implemented in routine clinical practice.
Topics: Baroreflex; Blood Pressure; Carotid Body; Electric Stimulation Therapy; Humans; Hypertension; Pressoreceptors; Prosthesis Implantation
PubMed: 32166464
DOI: 10.1007/s11906-020-1024-x -
The Journal of Physiology Apr 2020
Topics: Baroreflex; Blood Pressure; Humans; Hypertension, Pulmonary; Pressoreceptors; Sympathetic Nervous System
PubMed: 32096555
DOI: 10.1113/JP279662 -
The Journal of Physiology Mar 2020In an anaesthetised animal model, independent stimulation of baroreceptors in the pulmonary artery elicits reflex sympathoexcitation. In humans, pulmonary arterial...
KEY POINTS
In an anaesthetised animal model, independent stimulation of baroreceptors in the pulmonary artery elicits reflex sympathoexcitation. In humans, pulmonary arterial pressure is positively related to basal muscle sympathetic nerve activity (MSNA) under conditions where elevated pulmonary pressure is evident (e.g. high altitude); however, a causal link is not established. Using a novel experimental approach, we demonstrate that reducing pulmonary arterial pressure lowers basal MSNA in healthy humans. This response is distinct from the negative feedback reflex mediated by aortic and carotid sinus baroreceptors when systemic arterial pressure is lowered. Afferent input from pulmonary arterial baroreceptors may contribute to sympathetic neural activation in healthy lowland natives exposed to high altitude.
ABSTRACT
In animal models, distension of baroreceptors located in the pulmonary artery induces a reflex increase in sympathetic outflow; however, this has not been examined in humans. Therefore, we investigated whether reductions in pulmonary arterial pressure influenced sympathetic outflow and baroreflex control of muscle sympathetic nerve activity (MSNA). Healthy lowlanders (n = 13; 5 females) were studied 4-8 days following arrival at high altitude (4383 m; Cerro de Pasco, Peru), a setting that increases both pulmonary arterial pressure and sympathetic outflow. MSNA (microneurography) and blood pressure (BP; photoplethysmography) were measured continuously during ambient air breathing (Amb) and a 6 min inhalation of the vasodilator nitric oxide (iNO; 40 ppm in 21% O ), to selectively lower pulmonary arterial pressure. A modified Oxford test was performed under both conditions. Pulmonary artery systolic pressure (PASP) was determined using Doppler echocardiography. iNO reduced PASP (24 ± 3 vs. 32 ± 5 mmHg; P < 0.001) compared to Amb, with a similar reduction in MSNA total activity (1369 ± 576 to 994 ± 474 a.u min ; P = 0.01). iNO also reduced the MSNA operating point (burst incidence; 39 ± 16 to 33 ± 17 bursts·100 Hb ; P = 0.01) and diastolic operating pressure (82 ± 8 to 80 ± 8 mmHg; P < 0.001) compared to Amb, without changing heart rate (P = 0.6) or vascular-sympathetic baroreflex gain (P = 0.85). In conclusion, unloading of pulmonary arterial baroreceptors reduced basal sympathetic outflow to the skeletal muscle vasculature and reset vascular-sympathetic baroreflex control of MSNA downward and leftward in healthy humans at high altitude. These data suggest the existence of a lesser-known reflex input involved in sympathetic activation in humans.
Topics: Baroreflex; Blood Pressure; Female; Heart Rate; Humans; Hypertension, Pulmonary; Muscle, Skeletal; Pressoreceptors; Pulmonary Artery; Sympathetic Nervous System
PubMed: 31977069
DOI: 10.1113/JP278731 -
American Journal of Physiology.... Mar 2020The vestibular system contributes to regulating sympathetic nerve activity and blood pressure. Initial studies in decerebrate animals showed that neurons in the rostral...
The vestibular system contributes to regulating sympathetic nerve activity and blood pressure. Initial studies in decerebrate animals showed that neurons in the rostral ventrolateral medulla (RVLM) respond to small-amplitude (<10°) rotations of the body, as in other brain areas that process vestibular signals, although such movements do not affect blood distribution in the body. However, a subsequent experiment in conscious animals showed that few RVLM neurons respond to small-amplitude movements. This study tested the hypothesis that RVLM neurons in conscious animals respond to signals from the vestibular otolith organs elicited by large-amplitude static tilts. The activity of approximately one-third of RVLM neurons whose firing rate was related to the cardiac cycle, and thus likely received baroreceptor inputs, was modulated by vestibular inputs elicited by 40° head-up tilts in conscious cats, but not during 10° sinusoidal rotations in the pitch plane that affected the activity of neurons in brain regions providing inputs to the RVLM. These data suggest the existence of brain circuitry that suppresses vestibular influences on the activity of RVLM neurons and the sympathetic nervous system unless these inputs are physiologically warranted. We also determined that RVLM neurons failed to respond to a light cue signaling the movement, suggesting that feedforward cardiovascular responses do not occur before passive movements that require cardiovascular adjustments.
Topics: Action Potentials; Animals; Cats; Consciousness; Medulla Oblongata; Neurons; Pressoreceptors; Sympathetic Nervous System; Vestibule, Labyrinth
PubMed: 31940234
DOI: 10.1152/ajpregu.00205.2019 -
Scientific Reports Dec 2019Circulating levels of fibroblast growth factor-21 (FGF21) start increasing in patients with chronic kidney disease (CKD) since early stages during the cause of disease...
Circulating levels of fibroblast growth factor-21 (FGF21) start increasing in patients with chronic kidney disease (CKD) since early stages during the cause of disease progression. FGF21 is a liver-derived hormone that induces responses to stress through acting on hypothalamus to activate the sympathetic nervous system and the hypothalamus-pituitary-adrenal endocrine axis. However, roles that FGF21 plays in pathophysiology of CKD remains elusive. Here we show in mice that FGF21 is required to survive CKD but responsible for blood pressure dysregulation. When introduced with CKD, Fgf21 mice died earlier than wild-type mice. Paradoxically, these Fgf21 CKD mice escaped several complications observed in wild-type mice, including augmentation of blood pressure elevating response and activation of the sympathetic nervous system during physical activity and increase in serum noradrenalin and corticosterone levels. Supplementation of FGF21 by administration of an FGF21-expressing adeno-associated virus vector recapitulated these complications in wild-type mice and restored the survival period in Fgf21 CKD mice. In CKD patients, high serum FGF21 levels are independently associated with decreased baroreceptor sensitivity. Thus, increased FGF21 in CKD can be viewed as a survival response at the sacrifice of blood pressure homeostasis.
Topics: Animals; Blood Pressure; Disease Models, Animal; Fibroblast Growth Factors; Humans; Mice; Mice, Knockout; Pressoreceptors; Renal Insufficiency, Chronic
PubMed: 31848393
DOI: 10.1038/s41598-019-55643-4 -
Digestion 2020Transient receptor potential vanilloid 4 (TRPV4) is activated by stretch (mechanical), warm temperature, some epoxyeicosatrienoic acids, and lipopolysaccharide. TRPV4 is... (Review)
Review
Transient Receptor Potential Vanilloid 4 Regulation of Adenosine Triphosphate Release by the Adenosine Triphosphate Transporter Vesicular Nucleotide Transporter, a Novel Therapeutic Target for Gastrointestinal Baroreception and Chronic Inflammation.
BACKGROUND
Transient receptor potential vanilloid 4 (TRPV4) is activated by stretch (mechanical), warm temperature, some epoxyeicosatrienoic acids, and lipopolysaccharide. TRPV4 is expressed throughout the gastrointestinal epithelia and its activation induces adenosine triphosphate (ATP) exocytosis that is involved in visceral hypersensitivity. As an ATP transporter, vesicular nucleotide transporter (VNUT) mediates ATP storage in secretory vesicles and ATP release via exocytosis upon stimulation.
SUMMARY
TRPV4 is sensitized under inflammatory conditions by a variety of factors, including proteases and serotonin, whereas methylation-dependent silencing of TRPV4 expression is associated with various pathophysiological conditions. Gastrointestinal epithelia also release ATP in response to hypo-osmolality or acid through molecular mechanisms that remain unclear. These synergistically released ATP could be involved in visceral hypersensitivity. Low concentrations of the first generation bisphosphate, clodronate, were recently reported to inhibit VNUT activity and thus clodronate may be a safe and potent therapeutic option to treat visceral pain. Key Messages: This review focuses on: (1) ATP and TRPV4 activities in gastrointestinal epithelia; (2) factors that could modulate TRPV4 activity in gastrointestinal epithelia; and (3) the inhibition of VNUT as a potential novel therapeutic strategy for functional gastrointestinal disorders.
Topics: Abdominal Pain; Adenosine Triphosphate; Analgesics; Animals; Chronic Disease; Clodronic Acid; Gastrointestinal Tract; Humans; Inflammation; Mice; Mucous Membrane; Nucleotide Transport Proteins; Pressoreceptors; Receptors, Purinergic P2; TRPV Cation Channels
PubMed: 31770754
DOI: 10.1159/000504021 -
Cell Reports Nov 2019Mechanosensory neurons across physiological systems sense force using diverse terminal morphologies. Arterial baroreceptors are sensory neurons that monitor blood...
Mechanosensory neurons across physiological systems sense force using diverse terminal morphologies. Arterial baroreceptors are sensory neurons that monitor blood pressure for real-time stabilization of cardiovascular output. Various aortic sensory terminals have been described, but those that sense blood pressure are unclear because of a lack of selective genetic tools. Here, we find that all baroreceptor neurons are marked in Piezo2-ires-Cre mice and then use genetic approaches to visualize the architecture of mechanosensory endings. Cre-guided ablation of vagal and glossopharyngeal PIEZO2 neurons eliminates the baroreceptor reflex and aortic depressor nerve effects on blood pressure and heart rate. Genetic mapping reveals that PIEZO2 neurons form a distinctive mechanosensory structure: macroscopic claws that surround the aortic arch and exude fine end-net endings. Other arterial sensory neurons that form flower-spray terminals are dispensable for baroreception. Together, these findings provide structural insights into how blood pressure is sensed in the aortic vessel wall.
Topics: Animals; Autonomic Nervous System; Blood Pressure; Interoception; Mechanotransduction, Cellular; Mice; Neurons; Nodose Ganglion; Pressoreceptors; Vagus Nerve
PubMed: 31747594
DOI: 10.1016/j.celrep.2019.10.040 -
Cell Reports Nov 2019Soohong et al. (2019) reveal a class of vagal afferents-defined by Piezo2 expression-that innervate the aorta and function to sense blood pressure fluctuations. Their...
Soohong et al. (2019) reveal a class of vagal afferents-defined by Piezo2 expression-that innervate the aorta and function to sense blood pressure fluctuations. Their study describes the morphologies and role of these neurons in vascular regulation.
Topics: Animals; Aorta; Baroreflex; Blood Pressure; Hoof and Claw; Pressoreceptors
PubMed: 31747586
DOI: 10.1016/j.celrep.2019.11.031