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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 -
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 -
Scientific Reports Jul 2022Carotid baroreceptor stimulation has been clinically explored for antihypertensive benefits, but neuromodulation of aortic baroreceptor afferents remains unexplored for...
Carotid baroreceptor stimulation has been clinically explored for antihypertensive benefits, but neuromodulation of aortic baroreceptor afferents remains unexplored for potential translation into the clinic. Published studies have used supramaximal stimulations, which are unphysiological and energy inefficient. The objective of the present study was to identify optimal low-charge nerve stimulation parameters that would provide a clinically-relevant (20-30 mmHg) decrease in mean arterial pressure (MAP) in anesthetized spontaneously hypertensive rats. Stimulations of 20 s were delivered to the left aortic depressor nerve (ADN) of these rats using low ranges of pulse amplitudes (≤ 0.6 mA), widths (≤ 0.5 ms) and frequencies (≤ 5 Hz). We also assessed the effects of continuous (20 s) versus intermittent (5 s ON/3 s OFF and 5 s ON/3 s OFF for 20 s) stimulation on MAP, heart rate (HR), mesenteric (MVR) and femoral (FVR) vascular resistance using low (5 Hz) and high (15 Hz) frequencies. Lower pulse amplitudes (0.2 mA) produced 9 ± 2 to 18 ± 2 mmHg decreases in MAP. Higher pulse amplitudes (0.4 mA) produced a median MAP reduction of 28 ± 4 mmHg at 0.2 ms and 5 Hz, with no added benefit seen above 0.4 mA. Continuous and intermittent low frequency stimulation at 0.4 mA and 0.2 ms produced similar sustained decreases in MAP, HR, MVR and FVR. Continuous high frequency stimulation at 0.4 mA and 0.2 ms produced larger reductions in MAP, HR, MVR and FVR compared with all low frequency and/or intermittent high frequency stimulations. We conclude from these findings that "low intensity intermittent" electrical stimulation is an effective alternate way for neuromodulation of the aortic baroreceptor afferents and to evoke a required restoration of MAP levels in spontaneously hypertensive rats. This approach enables low energy consumption and markedly lowers the excessive decreases in MAP and hemodynamic disturbances elicited by continuous high-charge injection protocols.
Topics: Animals; Aorta; Blood Pressure; Electric Stimulation; Heart Rate; Hypertension; Pressoreceptors; Rats; Rats, Inbred SHR
PubMed: 35851099
DOI: 10.1038/s41598-022-15761-y -
Autonomic Neuroscience : Basic &... Sep 2022A reciprocal relationship between the baroreflex and cerebral autoregulation (CA) has been demonstrated at rest and in response to acute hypotension. We hypothesized... (Review)
Review
A reciprocal relationship between the baroreflex and cerebral autoregulation (CA) has been demonstrated at rest and in response to acute hypotension. We hypothesized that the reciprocal relationship between cardiac baroreflex sensitivity (BRS) and CA would be maintained during sustained central hypovolemia induced by lower body negative pressure (LBNP), and that the strength of this relationship would be greater in subjects with higher tolerance to this stress. Healthy young adults (n = 51; 23F/28M) completed a LBNP protocol to presyncope. Subjects were classified as high tolerant (HT; completion of -60 mmHg LBNP stage, ≥20-min) or low tolerant (LT; did not complete -60 mmHg LBNP stage, <20-min). R-R intervals (RRI), systolic arterial pressure (SAP), mean arterial pressure (MAP), and middle cerebral artery velocity (MCAv) were measured continuously. Cardiac BRS was calculated in the time domain (ΔHR/ΔSAP) and frequency domain (RRI-SAP low frequency (LF) transfer function gain), and CA was calculated in the time domain (ΔMCAv/ΔMAP) and frequency domain (MAP-mean MCAv LF transfer function gain). There was a moderate relationship between cardiac BRS and CA for the group of 51 subjects in both the time (R = -0.54, P < 0.0001) and frequency (R = 0.61, P < 0.001) domains; there was a stronger relationship in the HT group (R = 0.73) compared to the LT group (R = 0.31) in the frequency domain (P = 0.08), but no difference between groups in the time domain (HT: R = -0.73 vs. LT: R = -0.63; P = 0.27). These findings suggest that an interaction between BRS and CA may be an important compensatory mechanism that contributes to tolerance to simulated hemorrhage in young healthy adults.
Topics: Blood Pressure; Heart Rate; Hemorrhage; Homeostasis; Humans; Lower Body Negative Pressure; Pressoreceptors; Young Adult
PubMed: 35716525
DOI: 10.1016/j.autneu.2022.103007 -
Nutrients Feb 2022For normal maintenance of blood pressure and blood volume a well-balanced renin-angiotensin-aldosterone system (RAS) is necessary. For this purpose, renin is secreted as... (Review)
Review
For normal maintenance of blood pressure and blood volume a well-balanced renin-angiotensin-aldosterone system (RAS) is necessary. For this purpose, renin is secreted as the situation demands by the juxtaglomerular cells (also called as granular cells) that are in the walls of the afferent arterioles. Juxtaglomerular cells can sense minute changes in the blood pressure and blood volume and accordingly synthesize, store, and secrete appropriate amounts of renin. Thus, when the blood pressure and blood volume are decreased JGA cells synthesize and secrete higher amounts of renin and when the blood pressure and blood volume is increased the synthesis and secretion of renin is decreased such that homeostasis is restored. To decipher this important function, JGA cells (renin cells) need to sense and transmit the extracellular physical forces to their chromatin to control renin gene expression for appropriate renin synthesis. The changes in perfusion pressure are sensed by Integrin β1 that is transmitted to the renin cell's nucleus via lamin A/C that produces changes in the architecture of the chromatin. This results in an alteration (either increase or decrease) in renin gene expression. Cell membrane is situated in an unique location since all stimuli need to be transmitted to the cell nucleus and messages from the DNA to the cell external environment can be conveyed only through it. This implies that cell membrane structure and integrity is essential for all cellular functions. Cell membrane is composed to proteins and lipids. The lipid components of the cell membrane regulate its (cell membrane) fluidity and the way the messages are transmitted between the cell and its environment. Of all the lipids present in the membrane, arachidonic acid (AA) forms an important constituent. In response to pressure and other stimuli, cellular and nuclear shape changes occur that render nucleus to act as an elastic mechanotransducer that produces not only changes in cell shape but also in its dynamic behavior. Cell shape changes in response to external pressure(s) result(s) in the activation of cPLA2 (cytosolic phospholipase 2)-AA pathway that stretches to recruit myosin II which produces actin-myosin cytoskeleton contractility. Released AA can undergo peroxidation and peroxidized AA binds to DNA to regulate the expression of several genes. Alterations in the perfusion pressure in the afferent arterioles produces parallel changes in the renin cell membrane leading to changes in renin release. AA and its metabolic products regulate not only the release of renin but also changes in the vanilloid type 1 (TRPV1) expression in renal sensory nerves. Thus, AA and its metabolites function as intermediate/mediator molecules in transducing changes in perfusion and mechanical pressures that involves nuclear mechanotransduction mechanism. This mechanotransducer function of AA has relevance to the synthesis and release of insulin, neurotransmitters, and other soluble mediators release by specialized and non-specialized cells. Thus, AA plays a critical role in diseases such as diabetes mellitus, hypertension, atherosclerosis, coronary heart disease, sepsis, lupus, rheumatoid arthritis, and cancer.
Topics: Arachidonic Acid; Juxtaglomerular Apparatus; Mechanotransduction, Cellular; Pressoreceptors; Renin
PubMed: 35215399
DOI: 10.3390/nu14040749 -
JACC. Clinical Electrophysiology Feb 2022This study sought to evaluate the role of cardiac afferent reflexes in atrial fibrillation (AF).
OBJECTIVES
This study sought to evaluate the role of cardiac afferent reflexes in atrial fibrillation (AF).
BACKGROUND
Efferent autonomic tone is not associated with atrial remodeling and AF persistence. However, the role of cardiac afferents is unknown.
METHODS
Individuals with nonpermanent AF (n = 48) were prospectively studied (23 in the in-AF group and 25 in sinus rhythm [SR]) with 12 matched control subjects. We performed: 1) low-level lower body negative pressure (LBNP), which decreases cardiac volume, offloading predominantly cardiac afferent (volume-sensitive) low-pressure baroreceptors; 2) Valsalva reflex (predominantly arterial high-pressure baroreceptors); and 3) isometric handgrip reflex (both baroreceptors). We measured beat-to-beat mean arterial pressure (MAP) and heart rate (HR). LBNP elicits reflex vasoconstriction, estimated using venous occlusion plethysmography-derived forearm blood flow (∝1/vascular resistance), maintaining MAP. To assess reversibility, we repeated LBNP (same day) after 1-hour low-level tragus stimulation (in n = 5 in the in-AF group and n = 10 in the in-SR group) and >6 weeks post-cardioversion (n = 7).
RESULTS
The 3 groups were well matched for age (59 ± 12 years, 83% male), body mass index, and risk factors (P = NS). The in-AF group had higher left atrial volume (P < 0.001) and resting HR (P = 0.01) but similar MAP (P = 0.7). The normal LBNP vasoconstriction (-49 ± 5%) maintaining MAP (control subjects) was attenuated in the in-SR group (-12 ± 9%; P = 0.005) and dysfunctional in the in-AF group (+11 ± 6%; P < 0.001), in which MAP decreased and HR was unchanged. Valsalva was normal throughout. Handgrip MAP response was lowest in the in-AF group (P = 0.01). Interestingly, low-level tragus stimulation and cardioversion improved LBNP vasoconstriction (-48 ± 15%; P = 0.04; and -32 ± 9%; P = 0.02, respectively).
CONCLUSIONS
Cardiac afferent (volume-sensitive) reflexes are abnormal in AF patients during SR and dysfunctional during AF. This could contribute to AF progression, thus explaining "AF begets AF." (Characterisation of Autonomic function in Atrial Fibrillation [AF-AF Study]; ACTRN12619000186156).
Topics: Aged; Atrial Fibrillation; Female; Hand Strength; Heart Atria; Humans; Lower Body Negative Pressure; Male; Middle Aged; Pressoreceptors
PubMed: 35210071
DOI: 10.1016/j.jacep.2021.10.010 -
Advances in Physiology Education Jun 2022While the effects of changing heart rate and systemic vascular resistance have been generally understood and appreciated, the effects of changes in left ventricular... (Review)
Review
While the effects of changing heart rate and systemic vascular resistance have been generally understood and appreciated, the effects of changes in left ventricular contractility on end-systolic volume may have been less understood and appreciated and the effects of changes in venous capacitance on end-diastolic volume may have been unknown to many readers. Herein, we have provided a brief review for the medical student and beginning graduate student highlighting these sometimes-complex relationships.
Topics: Blood Pressure; Heart Rate; Heart Ventricles; Humans; Pressoreceptors; Vascular Resistance
PubMed: 35201919
DOI: 10.1152/advan.00160.2021 -
Acta Pharmacologica Sinica Sep 2022Recent studies suggest that melatonin (Mel) plays an important role in the regulation of blood pressure (BP) via the aortic baroreflex pathway. In this study, we...
Recent studies suggest that melatonin (Mel) plays an important role in the regulation of blood pressure (BP) via the aortic baroreflex pathway. In this study, we investigated the interaction between the baroreflex afferent pathway and Mel-mediated BP regulation in rats under physiological and hypertensive conditions. Mel (0.1, 0.3, and 1.0 mg/mL) was microinjected into the nodose ganglia (NG) of rats. We showed that Mel-induced reduction of mean arterial pressure in female rats was significantly greater than that in male and in ovariectomized rats under physiological condition. Consistently, the expression of Mel receptors (MTNRs) in the NG of female rats was significantly higher than that of males. In L-NAME-induced hypertensive and spontaneously hypertensive rat models, MTNRs were upregulated in males but downregulated in female models. Interestingly, Mel-induced BP reduction was found in male hypertensive models. In whole-cell recording from identified baroreceptor neurons (BRNs) in female rats, we found that Mel (0.1 μM) significantly increased the excitability of a female-specific subpopulation of Ah-type BRNs by increasing the Na1.9 current density via a PKC-mediated pathway. Similar results were observed in baroreceptive neurons of the nucleus tractus solitarius, showing the facilitation of spontaneous and evoked excitatory post-synaptic currents in Ah-type neurons. Collectively, this study reveals the estrogen-dependent effect of Mel/MTNRs under physiological and hypertensive conditions is mainly mediated by Ah-type BRNs, which may provide new theoretical basis and strategies for the gender-specific anti-hypertensive treatment in clinical practice.
Topics: Animals; Baroreflex; Blood Pressure; Estrogens; Female; Hypertension; Male; Melatonin; Pressoreceptors; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley
PubMed: 35132193
DOI: 10.1038/s41401-022-00867-w -
Journal of Integrative Neuroscience Dec 2021Here we use immunohistochemistry to examine the expression of Piezo2 in neurons of the mouse dorsal root ganglia and brain. Whereas Piezo2 is expressed in the large...
Piezo2-peripheral baroreceptor channel expressed in select neurons of the mouse brain: a putative mechanism for synchronizing neural networks by transducing intracranial pressure pulses.
Here we use immunohistochemistry to examine the expression of Piezo2 in neurons of the mouse dorsal root ganglia and brain. Whereas Piezo2 is expressed in the large majority (≥ 90%) of dorsal root ganglia neurons, Piezo2 expression is restricted to select neuron types in specific brain regions, including neocortical and hippocampal pyramidal neurons, cerebellar Purkinje cells and mitral cells of the olfactory bulb. Given the well-established role of Piezo2 as a low-threshold pressure sensor (i.e., ≤5 mmHg) in peripheral mechanosensation, including the regulation of breathing and blood pressure, its expression in central neurons has interesting implications. In particular, we hypothesize that Piezo2 provides neurons with an intrinsic resonance that promotes their entrainment by the normal intracranial pressure pulses (~5 mmHg) associated with breathing and cardiac cycles. The pressure-induced change in neural activity need only be very subtle to increase, for example, the robustness of respiration-entrained oscillations reported previously in widely distributed neuronal networks in both rodent and human brains. This idea of a "global brain rhythm" first arose from the effect of nasal airflow in activating mechanosensitive olfactory sensory neurons, which then synaptically entrain mitral cells within the olfactory bulb and through their projections, neural networks in other brain regions, including the hippocampus and neocortex. Our proposed, non-synaptic, intrinsic mechanism, where Piezo2 tracks the highly predictable and "metronome-like" intracranial pressure pulses-to date generally considered epiphenomena-would have the advantage that a physical force rapidly transmitted throughout the brain also contributes to this synchronization.
Topics: Animals; Biological Clocks; Hippocampus; Intracranial Pressure; Ion Channels; Male; Mice; Mice, Inbred C57BL; Neocortex; Nerve Net; Neurons; Pressoreceptors
PubMed: 34997707
DOI: 10.31083/j.jin2004085 -
BMJ Case Reports Dec 2021We present a case of a 77-year-old man who reported 5 months of syncopal episodes. He was found to have diffuse large B-cell lymphoma encasing the left internal...
We present a case of a 77-year-old man who reported 5 months of syncopal episodes. He was found to have diffuse large B-cell lymphoma encasing the left internal carotid artery but not impeding blood flow. The syncopal episodes resolved after his first cycle of chemotherapy. Recurrent syncope in non-cardiac lymphomas and other head and neck masses is exceedingly rare and may be due to reflex syncope prompted by carotid baroreceptor activation. There are 11 previously described cases of recurrent syncope associated with non-cardiac lymphoma. In all cases, lymphadenopathy abutting the carotid artery was present and the syncopal episodes resolved with treatment. Our case illustrates that malignancy should be considered in patients with unexplained recurrent syncope.
Topics: Aged; Carotid Artery, Internal; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Neoplasm Recurrence, Local; Pressoreceptors; Syncope
PubMed: 34969790
DOI: 10.1136/bcr-2021-244881