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Science (New York, N.Y.) Feb 2024A central baroreceptor monitors arterial pressure to modulate brain activity.
A central baroreceptor monitors arterial pressure to modulate brain activity.
Topics: Blood Pressure; Brain; Heart; Heart Rate; Pressoreceptors; Animals; Mice; Rats
PubMed: 38301020
DOI: 10.1126/science.adn4942 -
Neurological Sciences : Official... Jan 2021Initial cardiovascular fingolimod effects might compromise baroreflex responses to rapid blood pressure (BP) changes during common Valsalva-like maneuvers. This study...
BACKGROUND AND PURPOSE
Initial cardiovascular fingolimod effects might compromise baroreflex responses to rapid blood pressure (BP) changes during common Valsalva-like maneuvers. This study evaluated cardiovascular responses to Valsalva maneuver (VM)-induced baroreceptor unloading and loading upon fingolimod initiation.
PATIENTS AND METHODS
Twenty-one patients with relapsing-remitting multiple sclerosis performed VMs before and 0.5, 1, 2, 3, 4, 5, and 6 hours after fingolimod initiation. We recorded heart rate (HR) as RR intervals (RRI), systolic and diastolic BP (BPsys, BPdia) during VM phase 1, VM phase 2 early, VM phase 2 late, and VM phase 4. Using linear regression analysis between decreasing BPsys and RRI values during VM phase 2 early, we determined baroreflex gain (BRG) reflecting vagal withdrawal and sympathetic activation upon baroreceptor unloading. To assess cardiovagal activation upon baroreceptor loading, we calculated Valsalva ratios (VR) between maximal and minimal RRIs after strain release. Analysis of variance or Friedman tests with post hoc analysis compared corresponding parameters at the eight time points (significance: p < 0.05).
RESULTS
RRIs at VM phase 1, VM phase 2 early, and VM phase 2 late were higher after than before fingolimod initiation, and maximal after 4 hours. Fingolimod did not affect the longest RRIs upon strain release, but after 3, 5, and 6 hours lowered the highest BPsys values during overshoot and all BPdia values, and thus reduced VRs. BRG was slightly higher after 3 and 5 hours, and significantly higher after 4 hours than before fingolimod initiation.
CONCLUSIONS
VR-decreases 3-6 hours after fingolimod initiation are physiologic results of fingolimod-associated attenuations of BP and HR increases at the end of strain and do not suggest impaired cardiovagal activation upon baroreceptor loading. Stable and at the time of HR nadir significantly increased BRGs indicate improved responses to baroreceptor unloading. Thus, cardiovascular fingolimod effects do not impair autonomic responses to sudden baroreceptor loading or unloading but seem to be mitigated by baroreflex resetting.
Topics: Baroreflex; Blood Pressure; Fingolimod Hydrochloride; Heart Rate; Humans; Pressoreceptors; Valsalva Maneuver
PubMed: 33443674
DOI: 10.1007/s10072-020-05004-1 -
Pflugers Archiv : European Journal of... Aug 2023Reflex summation in the expression of left and right aortic baroreflex control of hemodynamic functions was investigated. In anesthetized Sprague-Dawley rats, mean...
Reflex summation in the expression of left and right aortic baroreflex control of hemodynamic functions was investigated. In anesthetized Sprague-Dawley rats, mean arterial pressure (MAP), heart rate (HR), and mesenteric vascular resistance (MVR) were recorded following left, right, and bilateral stimulation of the aortic depressor nerve (ADN). Stimulation frequency was varied between low (1 Hz), moderate (5 Hz), and high (20 Hz). At 1 Hz, left and right ADN stimulation evoked similar depressor, bradycardic and MVR responses, whereas bilateral stimulation induced larger MAP, HR, and MVR reductions compared with stimulations of either side. The sum of the separate and combined stimulation effects on MAP, HR, and MVR was similar, indicating an additive summation. A similar additive summation was observed with HR responses at 5 and 20 Hz. Left-sided and bilateral stimulation produced greater depressor and MVR responses than right-sided stimulation, with responses of the bilateral stimulation mimicking those of the left side. The bilateral MAP or MVR response was smaller than the sum of the separate responses, suggesting an inhibitory summation. In conclusion, reflex summation of the left and right aortic baroreceptor afferent input is differentially expressed in relation to the frequency of the input signal. Summation of baroreflex control of HR is always additive and independent of stimulation frequency. Summation of baroreflex control of MAP is additive when the frequency input is small and inhibitory when the frequency input is moderate to high, with MAP changes mainly driven by parallel baroreflex-triggered changes in vascular resistance.
Topics: Rats; Animals; Pressoreceptors; Rats, Sprague-Dawley; Blood Pressure; Electric Stimulation; Reflex; Baroreflex; Heart Rate
PubMed: 37219603
DOI: 10.1007/s00424-023-02820-0 -
Circulation. Arrhythmia and... Apr 2021Symptomatic heart failure (HF) patients despite optimal medical therapy and advances such as invasive hemodynamic monitoring remain challenging to manage. While cardiac... (Review)
Review
Symptomatic heart failure (HF) patients despite optimal medical therapy and advances such as invasive hemodynamic monitoring remain challenging to manage. While cardiac resynchronization therapy remains a highly effective therapy for a subset of HF patients with wide QRS, a majority of symptomatic HF patients are poor candidates for such. Recently, cardiac contractility modulation, neuromodulation based on carotid baroreceptor stimulation, and phrenic nerve stimulation have been approved by the US Food and Drug Administration and are emerging as therapeutic options for symptomatic HF patients. This state-of-the-art review examines the role of these evolving electrical therapies in advanced HF.
Topics: Animals; Autonomic Nervous System; Cardiac Pacing, Artificial; Electric Stimulation Therapy; Heart; Heart Failure; Humans; Myocardial Contraction; Pacemaker, Artificial; Prevalence; Recovery of Function; Spinal Cord Stimulation; Stroke Volume; Treatment Outcome; Vagus Nerve Stimulation; Ventricular Function, Left
PubMed: 33858178
DOI: 10.1161/CIRCEP.120.009668 -
Obesity (Silver Spring, Md.) Jun 2023Sympathetic nervous system overactivation and abnormal lipid metabolism are featured in obesity and may lead to cardiac remodeling. The effects of carotid baroreceptor...
OBJECTIVE
Sympathetic nervous system overactivation and abnormal lipid metabolism are featured in obesity and may lead to cardiac remodeling. The effects of carotid baroreceptor stimulation (CBS) on cardiac remodeling in obese rats and the underlying mechanisms were explored.
METHODS
An obesity model was induced by 16-week high-fat diet feeding. A CBS device was implanted at the 8th week. Body weight and blood pressure measurements, electrocardiography, echocardiography, and glucose and insulin tolerance tests were conducted before sampling. Plasma analysis and histological and biological analyses of left ventricle were also performed. Neonatal rat cardiomyocytes cocultured with 3T3-L1 in transwell chambers were used to investigate the mechanisms.
RESULTS
CBS alleviated several manifestations of obesity, including increased body weight, high blood pressure, hyperlipidemia, and enhanced sympathetic activity. In obese hearts, norepinephrine levels decreased, and the monoamine oxidase A (MAO-A) and reactive oxygen species level increased; these changes, as well as cardiac fibrosis, lipid metabolic disorders, and heart dysfunction, were inhibited by CBS. Neonatal rat cardiomyocytes incubated with norepinephrine showed MAO-A upregulation, increased reactive oxygen species levels, lipid metabolic disorders, and inflammatory response, which were inhibited by clorgyline, a selective MAO-A inhibitor.
CONCLUSIONS
CBS effectively suppresses sympathetic nervous system activity and oxidative stress mediated by MAO-A and prevents cardiac remodeling in obese rats.
Topics: Rats; Animals; Monoamine Oxidase; Pressoreceptors; Reactive Oxygen Species; Ventricular Remodeling; Oxidative Stress; Obesity; Lipids; Norepinephrine
PubMed: 36998154
DOI: 10.1002/oby.23729 -
Linear and nonlinear identification of the carotid sinus baroreflex in the very low-frequency range.Physiological Reports Jul 2022Since the arterial baroreflex system is classified as an immediate control system, the focus has been on analyzing its dynamic characteristics in the frequency range...
Since the arterial baroreflex system is classified as an immediate control system, the focus has been on analyzing its dynamic characteristics in the frequency range between 0.01 and 1 Hz. Although the dynamic characteristics in the frequency range below 0.01 Hz are not expected to be large, actual experimental data are scant. The aim was to identify the dynamic characteristics of the carotid sinus baroreflex in the frequency range down to 0.001 Hz. The carotid sinus baroreceptor regions were isolated from the systemic circulation, and carotid sinus pressure (CSP) was changed every 10 s according to Gaussian white noise with a mean of 120 mmHg and standard deviation of 20 mmHg for 90 min in anesthetized Wistar-Kyoto rats (n = 8). The dynamic gain of the linear transfer function relating CSP to arterial pressure (AP) at 0.001 Hz tended to be greater than that at 0.01 Hz (1.060 ± 0.197 vs. 0.625 ± 0.067, p = 0.080), suggesting that baroreflex control was largely maintained at 0.001 Hz. Regarding nonlinear analysis, a second-order Uryson model predicted AP with a higher R value (0.645 ± 0.053) than a linear model (R = 0.543 ± 0.057, p = 0.025) or a second-order Volterra model (R = 0.589 ± 0.055, p = 0.045) in testing data. These pieces of information may be used to create baroreflex models that can add a component of autonomic control to a cardiovascular digital twin for predicting acute hemodynamic responses to treatments and tailoring individual treatment strategies.
Topics: Animals; Arterial Pressure; Baroreflex; Blood Pressure; Carotid Sinus; Pressoreceptors; Rats; Rats, Inbred WKY; Sympathetic Nervous System
PubMed: 35859325
DOI: 10.14814/phy2.15392 -
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 -
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 -
Clinical and Experimental Rheumatology Oct 2022Systemic sclerosis (SSc) is an autoimmune disease characterised by diffuse vasculopathy and fibrosis of skin and visceral organs. Moreover, autonomic dysfunction is also...
OBJECTIVES
Systemic sclerosis (SSc) is an autoimmune disease characterised by diffuse vasculopathy and fibrosis of skin and visceral organs. Moreover, autonomic dysfunction is also suggested as an important step during the multifactorial SSc pathogenesis. Baroreceptors are responsible for maintaining blood pressure by means of autonomic system modulation. Considering that autonomic dysfunction and arteriosclerosis can both reduce baroreceptor sensitivity (BRS), in this cross-sectional study we investigated BRS in SSc patients.
METHODS
Twenty-one SSc patients (mean age 55±10 years, 18 females) and 147 age/sex-matched healthy controls were recruited for the study. BRS (ms/mmHg) was measured by a Finapres® Midi device (Finapres Medical Systems, Amsterdam, The Netherlands). Other parameters were measured: blood pressure, heart rate, heart rate variability triangular index (HRVI), intima-media thickness (IMT), carotid distensibility and pulse wave velocity (PWV).
RESULTS
BRS was significantly lower in SSc patients compared to controls (6.3±3.3 vs. 10.7±6.8 ms/mmHg; p=0.004). IMT was comparable between SSc and controls, whereas carotid distensibility was lower in SSc (20.1±7.6 vs. 26.6±13.3 KPa-1·10-3; p=0.02) and PWV higher in SSc (8.4±1.3 vs. 7.1±1.1 m/sec; p=0.01). Furthermore, HRVI was lower in SSc (4.5±2.1 vs. 7.5±2.8; p<0.001). BRS impairment was independent from age and carotid distensibility in SSc patients, suggesting that BRS dysfunction could be only partially a consequence of SSc vasculopathy.
CONCLUSIONS
BRS was reduced in SSc patients compared with healthy controls. This finding could represent a SSc-related alteration involving the autonomic system, besides being the mere consequence of sclerodermic vasculopathy.
Topics: Female; Humans; Middle Aged; Aged; Pressoreceptors; Pulse Wave Analysis; Carotid Intima-Media Thickness; Cross-Sectional Studies; Carotid Arteries; Scleroderma, Systemic; Vascular Diseases
PubMed: 35916301
DOI: 10.55563/clinexprheumatol/4j6028