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1.
Philos Trans A Math Phys Eng Sci ; 379(2212): 20200263, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34689615

RESUMO

Assessing Granger causality (GC) intended as the influence, in terms of reduction of variance of surprise, that a driver variable exerts on a given target, requires a suitable treatment of 'instantaneous' effects, i.e. influences due to interactions whose time scale is much faster than the time resolution of the measurements, due to unobserved confounders or insufficient sampling rate that cannot be increased because the mechanism of generation of the variable is inherently slow (e.g. the heartbeat). We exploit a recently proposed framework for the estimation of causal influences in the spectral domain and include instantaneous interactions in the modelling, thus obtaining (i) a novel index of undirected instantaneous causality and (ii) a novel measure of GC including instantaneous effects. An effective procedure to speed up the optimization of parameters in this frame is also presented. After illustrating the proposed formalism in a theoretical example, we apply it to two datasets of cardiovascular and respiratory time series and compare the values obtained within the frequency bands of physiological interest by the proposed total measure of causality with those derived from the standard GC analysis. We find that the inclusion of instantaneous causality allows us to correctly disentangle the baroreflex mechanism from the effects related to cardiorespiratory interactions. Moreover, studying how controlling the respiratory rhythm acts on cardiovascular interactions, we document an increase of the direct (non-baroreflex mediated) influence of respiration on the heart rate in the respiratory frequency band when switching from spontaneous to paced breathing. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.


Assuntos
Algoritmos , Barorreflexo , Simulação por Computador , Frequência Cardíaca
2.
Arq Bras Cardiol ; 117(2): 290-297, 2021 08.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34495221

RESUMO

BACKGROUND: Nucleus tractus solitarius (NTS) is a brain area that plays a key role in kidney and cardiovascular regulation via baroreceptors impulses. OBJECTIVES: The aim of this study was to evaluate the effect of naringin (NAR) and trimetazidine (TMZ) alone and their combination on NTS electrical activity and baroreceptor sensitivity (BRS) in renal ischemia- reperfusion (I/R) injury. METHODS: Forty male Sprague-Dawley rats (200- 250 g) were allocated into 5 groups with 8 in each. 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; and 5) TMZ5+ NAR100. The left femoral vein was cannulated to infuse saline solution or drug and the BRS was evaluated. I/R was induced by occlusion of renal pedicles for 45 min, followed by 4 hours of reperfusion. The NTS local electroencephalogram (EEG) was recorded before, during ischemia and throughout the reperfusion. Phenylephrine was injected intravenously to evaluate BRS at the end of reperfusion time. The data were analyzed by two-way repeated measurement ANOVA followed by Tukey's post hoc test. A p-value <0.05 was considered significant. RESULTS: NTS electrical waves did not change during ischemia time, while they significantly decreased during the entire reperfusion time. NTS electrical activity and BRS dramatically reduced in rats with I/R injury; however, administration of NAR, TMZ alone or their combination significantly improved these changes in rats with I/R injury. CONCLUSIONS: The results showed that I/R injury leads to reduced BRS and NTS electrical activity and there may be an association between I/R and decreased BRS. In addition, NAR and TMZ are promising agents to treat I/R complications.


Assuntos
Traumatismo por Reperfusão , Trimetazidina , Animais , Barorreflexo , Flavanonas , Rim , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Núcleo Solitário , Trimetazidina/farmacologia
4.
Int J Psychophysiol ; 169: 71-87, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34534600

RESUMO

Interoception, the ability to perceive internal bodily sensations, and heart rate variability (HRV) share common physiological pathways, including the baroreflex feedback loop. The baroreflex can be activated by resonance breathing, wherein respiration is paced at 6 times per minute (0.1 Hz), eliciting immediate physiological changes and longer-term therapeutic responses. This registered report characterizes baroreflex functioning as a cardiac mechanism of interoception in a two-session study (n = 67). The heartbeat discrimination task was used to obtain indices of interoceptive accuracy, sensibility and metacognition. Baroreflex functioning was measured as HRV at 0.1 Hz and baroreflex sensitivity (BRS); high frequency (HF) HRV was calculated as a control. Cardiovascular indices were measured at baseline and during active and control paced breathing after which changes in interoception were measured. The first hypothesis was that baseline baroreflex functioning would predict individual differences in interoceptive awareness. The second hypothesis was that resonance breathing would increase participants' ability to detect their own heartbeats, and that this effect would be mediated by increases in 0.1 Hz HRV and BRS. Data were collected upon in principle acceptance of the manuscript. We found a negative relationship of interoceptive accuracy with baseline HF HRV and BRS, and a positive relationship between metacognitive interoception and 0.1HZ HRV, BRS and HF HRV. We found that changes in 0.1 Hz HRV and BRS during resonance breathing positively correlate with increases in interoceptive accuracy. Our results show that the extent to which breathing recruits the resonant properties of the cardiovascular system can facilitate the conscious perception of participants' heartbeats. We interpret this as an increase in vagal afferent signaling and baroreflex functioning following resonance breathing. We put forward an alternative explanation that HRV modulation can reduce interoceptive prediction errors, facilitating the conscious perception of interoceptive signals, and consider the role of resonance breathing on mental health from an interoceptive inference perspective.


Assuntos
Barorreflexo , Interocepção , Conscientização , Coração , Frequência Cardíaca , Humanos , Respiração
5.
J Comp Physiol B ; 191(5): 917-925, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34363512

RESUMO

In humans, physical exercise imposes narrower limits for the heart rate (fH) response of the baroreflex, and vascular modulation becomes largely responsible for arterial pressure regulation. In undisturbed reptiles, the baroreflex-related fH alterations at the operating point (Gop) decreases at elevated body temperatures (Tb) and the vascular regulation changes accordingly. We investigated how the baroreflex of rattlesnakes, Crotalus durissus, is regulated during an activity at different Tb, expecting that activity would reduce the capacity of the cardiac baroreflex neural pathway to buffer arterial pressure fluctuations while being compensated by the vascular neural pathway regulation. Snakes were catheterized for blood pressure assessment at three different Tb: 15, 20 and 30 °C. Data were collected before and after activity at each Tb. Baroreflex gain (Gop) was assessed with the sequence method; the vascular limb, with the time constant of pressure decay (τ), using the two-element Windkessel equation. Both Gop and τ reduced when Tb increased. Activity also reduced Gop and τ in all Tb. The relationship between τ and pulse interval (τ/PI) was unaffected by the temperature at resting snakes, albeit it reduced after activity at 20 °C and 30 °C. The unchanged τ/PI and normalized Gop at different Tb indicated those variables are actively adjusted to work at different fH and pressure conditions at rest. Our data suggest that during activity, the baroreflex-related fH response is attenuated and hypertension is buffered by a disproportional increase in the rate which pressure decays during diastole. This compensation seems especially important at higher Tb where Gop is already low.


Assuntos
Barorreflexo , Crotalus , Animais , Pressão Sanguínea , Frequência Cardíaca , Humanos , América do Sul , Temperatura
6.
Am J Physiol Regul Integr Comp Physiol ; 321(4): R525-R536, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34378422

RESUMO

The effects of nitroglycerin (glyceryl trinitrate, GTN) on baroreflex sensitivity (BRS) are incompletely understood. Moreover, there are no reports evaluating the acute responses in both the sympathetic BRS (SBRS) and the cardiovagal BRS (CBRS) to the administration of sublingual GTN. We hypothesized that sublingual GTN modulates both CBRS and SBRS. In 10 healthy subjects, beat-to-beat heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were recorded before and for 10 min after sublingual administration of GTN 0.4 mg. SBRS was evaluated from the relationship between spontaneous variations in diastolic BP and MSNA. CBRS was assessed with the sequence technique. These variables were assessed during baseline, during 3rd-6th min (post A), and 7th-10th min (post B) after GTN administration. Two min after GTN administration, MSNA increased significantly and remained significantly elevated during recording. Compared with baseline, CBRS decreased significantly (post A: 12.9 ± 1.6 to 7.1 ± 1.0 ms/mmHg, P < 0.05), whereas SBRS increased significantly (post A: 0.8 ± 0.2 to 1.5 ± 0.2 units·beat-1·mmHg-1, P < 0.05) with an upward shift of the operating point. There were no differences in these variables between posts A and B. A clinical dose of GTN increased MSNA rapidly through effects on both CBRS and SBRS. These effects should be kept in mind when nitrates are used to clinically treat chest pain and acute coronary syndromes and used as vasodilators in experimental settings.


Assuntos
Barorreflexo/efeitos dos fármacos , Coração/inervação , Músculo Esquelético/inervação , Nitroglicerina/administração & dosagem , Sistema Nervoso Simpático/efeitos dos fármacos , Nervo Vago/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Administração Sublingual , Pressão Sanguínea/efeitos dos fármacos , Feminino , Voluntários Saudáveis , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Nervoso Simpático/fisiologia , Nervo Vago/fisiologia
7.
Am J Physiol Regul Integr Comp Physiol ; 321(2): R260-R270, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34231375

RESUMO

Previous studies have demonstrated that sympathetic baroreflex sensitivity (BRS) increases during orthostatic stress in humans. We recently showed that dietary salt intake affects sympathetic neural control in healthy premenopausal women. This study aimed to determine whether salt loading versus salt reduction would impact sympathetic BRS during orthostasis in premenopausal women with a history of normal pregnancy. Nine healthy women [42 ± 3 (SD) yr] were given a standardized isocaloric high-salt (250 mEq sodium/day) or low-salt (50 mEq sodium/day) diet for 1 wk each (∼2 mo apart with the order randomized), whereas water intake was ad libitum. Laboratory testing was performed following each high- and low-salt period in the midluteal phase of the menstrual cycle. Hemodynamics and muscle sympathetic nerve activity (MSNA) were measured at baseline (supine; 2 min) and during a graded head-up tilt (30° for 5 min and 60° for 20 min). Sympathetic BRS was assessed during baseline and head-up tilt. Hemodynamics were not different between salt conditions during baseline or tilt. Both supine and upright MSNA indices were lower in high salt than low salt (all P < 0.05), however, there was no interaction effect (P = 0.507-0.996). On moving from supine to upright, sympathetic BRS remained unchanged in high salt but increased in low salt (P = 0.028 for interaction). Thus, salt loading diminishes the responsiveness of sympathetic BRS during orthostasis compared with salt reduction in healthy premenopausal women with prior normal pregnancy. Whether this is one underlying mechanism for salt-induced development of hypertension during ambulation remains to be determined.


Assuntos
Barorreflexo , Dieta Hipossódica , Tontura/fisiopatologia , Hemodinâmica , Músculo Esquelético/inervação , Cloreto de Sódio na Dieta/efeitos adversos , Sistema Nervoso Simpático/fisiopatologia , Adulto , Pressão Sanguínea , Estudos Cross-Over , Tontura/diagnóstico , Feminino , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Gravidez , Distribuição Aleatória , Texas , Teste da Mesa Inclinada , Fatores de Tempo
8.
J Appl Physiol (1985) ; 131(2): 794-807, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197227

RESUMO

The baroreflex integrity in early-stage pulmonary arterial hypertension (PAH) remains uninvestigated. A potential baroreflex impairment could be functionally relevant and possibly mediated by enhanced peripheral chemoreflex activity. Thus, we investigated 1) the cardiac baroreflex in nonhypoxemic PAH; 2) the association between baroreflex indexes and peak aerobic capacity [i.e., peak oxygen consumption (V̇o2peak)]; and 3) the peripheral chemoreflex contribution to the cardiac baroreflex. Nineteen patients and 13 age- and sex-matched healthy adults (HA) randomly inhaled either 100% O2 (peripheral chemoreceptor inhibition) or 21% O2 (control session) while at rest and during a repeated sit-to-stand maneuver. Beat-by-beat analysis of R-R intervals and systolic blood pressure provided indexes of cardiac baroreflex sensitivity (cBRS) and effectiveness (cBEI). The PAH group had lower cBEI for all sequences (cBEIALL) at rest [means ± SD: PAH = 0.5 ± 0.2 vs. HA = 0.7 ± 0.1 arbitrary units (a.u.), P = 0.02] and lower cBRSALL (PAH = 6.8 ± 7.0 vs. HA = 9.7 ± 5.0 ms·mmHg-1, P < 0.01) and cBEIALL (PAH = 0.4 ± 0.2 vs. HA= 0.6 ± 0.1 a.u., P < 0.01) during the sit-to-stand maneuver versus the HA group. The cBEI during the sit-to-stand maneuver was independently correlated to V̇o2peak (partial r = 0.45, P < 0.01). Hyperoxia increased cBRS and cBEI similarly in both groups at rest and during the sit-to-stand maneuver. Therefore, cardiac baroreflex dysfunction was observed under spontaneous and, most notably, provoked blood pressure fluctuations in nonhypoxemic PAH, was not influenced by the peripheral chemoreflex, and was associated with lower V̇o2peak, suggesting that it could be functionally relevant.NEW & NOTEWORTHY Does the peripheral chemoreflex play a role in cardiac baroreflex dysfunction in patients with pulmonary arterial hypertension (PAH)? Here we provide new evidence of cardiac baroreflex dysfunction under spontaneous and, most notably, provoked blood pressure fluctuations in patients with nonhypoxemic PAH. Importantly, impaired cardiac baroreflex effectiveness during provoked blood pressure fluctuations was independently associated with poorer functional capacity. Finally, our results indicated that the peripheral chemoreflex did not mediate cardiac baroreflex dysfunction among those patients.


Assuntos
Barorreflexo , Hipertensão Arterial Pulmonar , Pressão Sanguínea , Células Quimiorreceptoras , Frequência Cardíaca , Humanos
9.
Physiol Meas ; 42(8)2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34261052

RESUMO

Objective.To investigate the interplay between active standing and heat stress on cardiovascular autonomic modulation in healthy individuals.Approach.Blood pressure (BP) and ECG were continuously recorded during 30 min in supine (SUP) and 6 min in orthostatic position (ORT) under thermal reference (TC; ∼24 °C) or heated environment (HOT; ∼36 °C) conditions, in a randomized order. All data collection was performed during the winter and spring seasons when typical outdoor temperatures are ∼23 °C. Spectral analysis was employed by the autoregressive model of R-R and systolic blood pressure (SBP) time series and defined, within each band, in low (LF, 0.04 to 0.15 Hz) and high (0.15-0.40 Hz) frequencies. The indices of cardiac sympathetic (LF) and cardiac parasympathetic (HF) were normalized (nu) dividing each band power by the total power subtracted the very-low component (<0.04 Hz), obtaining the cardiac autonomic balance (LF/HF) modulation. The gain of the relationship between SBP and R-R variabilities within the LF band was utilized for analysis of spontaneous baroreflex sensitivity (alpha index;αLF). Nonlinear analysis was employed through symbolic dynamics of R-R, which provided the percentage of sequences of three heart periods without changes in R-R interval (0V%; cardiac sympathetic modulation) and two significant variations (2UV% and 2LV%; cardiac vagal modulation).Main results.HOT increased 0V% and HR, and decreasedαLF and 2UV% during SUP compared to TC. During ORT, HOT provokes a greater increment on HR, LF/HF and 0V%, indexes compared to ORT under TC.Significance.At rest, heat stress influences both autonomic branches, increasing sympathetic and decreasing vagal modulation and spontaneous baroreflex sensitivity. The augmented HR during active standing under heat stress seems to be mediated by a greater increment in cardiac sympathetic modulation, showing an interplay between gravitational and thermal stimulus.


Assuntos
Sistema Nervoso Autônomo , Sistema Cardiovascular , Barorreflexo , Pressão Sanguínea , Frequência Cardíaca , Humanos
10.
Artigo em Inglês | MEDLINE | ID: mdl-34209901

RESUMO

The effects of androgen anabolic steroids (AAS) use on athletes' cardiac autonomic activity in terms of baroreflex sensitivity (BRS), and heart rate variability (HRV) have not yet been adequately studied. Furthermore, there is no information to describe the possible relationship between the structural and functional cardiac remodeling and the cardiac autonomic nervous system changes caused by AAS abuse. Thus, we aimed to study the effects of long-term AAS abuse on cardiac autonomic efficacy and cardiac adaptations in strength-trained athletes. In total, 80 strength-trained athletes (weightlifters and bodybuilders) participated in the study. Notably, 40 of them using AAS according to their state formed group A, 40 nonuser strength-trained athletes comprised group B, and 40 healthy nonathletes (group C) were used as controls. All subjects underwent a head-up tilt test using the 30 min protocol to evaluate the baroreflex sensitivity and short HRV modulation. Furthermore, all athletes undertook standard echocardiography, a cardiac tissue Doppler imaging (TDI) study, and a maximal spiroergometric test on a treadmill to estimate their maximum oxygen consumption (VO2max). The tilt test results showed that group A presented a significantly lower BRS and baroreflex effectiveness index than group B by 13.8% and 10.7%, respectively (p < 0.05). Regarding short-term HRV analysis, a significant increase was observed in sympathetic activity in AAS users. Moreover, athletes of group A showed increased left ventricular (LV) mass index (LVMI) by 8.9% (p < 0.05), compared to group B. However, no difference was found in LV ejection fraction between the groups. TDI measurements indicated that AAS users had decreased septal and lateral peak E' by 38.0% (p < 0.05) and 32.1% (p < 0.05), respectively, and increased E/E' by 32.0% (p < 0.05), compared to group B. This LV diastolic function alteration was correlated with the year of AAS abuse. A significant correlation was established between BRS depression and LV diastolic impairment in AAS users. Cardiopulmonary test results showed that AAS users had significantly higher time to exhaustion by 11.0 % (p < 0.05) and VO2max by 15.1% (p < 0.05), compared to controls. A significant correlation was found between VO2max and LVMI in AAS users. The results of the present study indicated that long-term AAS use in strength-trained athletes led to altered cardiovascular autonomic modulations, which were associated with indices of early LV diastolic dysfunction.


Assuntos
Anabolizantes , Barorreflexo , Anabolizantes/efeitos adversos , Ecocardiografia , Humanos , Esteroides , Congêneres da Testosterona
11.
Cells ; 10(5)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069822

RESUMO

Sodium salicylate (SA), a cyclooxygenase inhibitor, has been shown to increase insulin sensitivity and to suppress inflammation in obese patients and animal models. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed in afferent nerve fibers. Cyclooxygenase-derived prostaglandins are involved in the activation and sensitization of TRPV1. This study tested whether the metabolic and renal effects of SA were mediated by the TRPV1 channel. Wild-type (WT) and TRPV1-/- mice were fed a Western diet (WD) for 4 months and received SA infusion (120mg/kg/day) or vehicle for the last 4 weeks of WD feeding. SA treatment significantly increased blood pressure in WD-fed TRPV1-/- mice (p < 0.05) but not in WD-fed WT mice. Similarly, SA impaired renal blood flow in TRPV1-/- mice (p < 0.05) but not in WT mice. SA improved insulin and glucose tolerance in both WT and TRPV1-/- mice on WD (all p < 0.05). In addition, SA reduced renal p65 and urinary prostaglandin E2, prostaglandin F1α, and interleukin-6 in both WT and TRPV1-/- mice (all p < 0.05). SA decreased urine noradrenaline levels, increased afferent renal nerve activity, and improved baroreflex sensitivity in WT mice (all p < 0.05) but not in TRPV1-/- mice. Importantly, SA increased serum creatinine and urine kidney injury molecule-1 levels and decreased the glomerular filtration rate in obese WT mice (all p < 0.05), and these detrimental effects were significantly exacerbated in obese TRPV1-/- mice (all p < 0.05). Lastly, SA treatment increased urine albumin levels in TRPV1-/- mice (p < 0.05) but not in WT mice. Taken together, SA-elicited metabolic benefits and anti-inflammatory effects are independent of TRPV1, while SA-induced sympathetic suppression is dependent on TRPV1 channels. SA-induced renal dysfunction is dependent on intact TRPV1 channels. These findings suggest that SA needs to be cautiously used in patients with obesity or diabetes, as SA-induced renal dysfunction may be exacerbated due to impaired TRPV1 in obese and diabetic patients.


Assuntos
Inibidores de Ciclo-Oxigenase/toxicidade , Dieta Hiperlipídica , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Obesidade/tratamento farmacológico , Salicilato de Sódio/toxicidade , Sistema Nervoso Simpático/efeitos dos fármacos , Canais de Cátion TRPV/deficiência , Animais , Barorreflexo/efeitos dos fármacos , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Deleção de Genes , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Resistência à Insulina , Rim/inervação , Rim/metabolismo , Nefropatias/metabolismo , Nefropatias/fisiopatologia , Nefropatias/prevenção & controle , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/complicações , Obesidade/metabolismo , Obesidade/fisiopatologia , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia , Canais de Cátion TRPV/genética
12.
Cells ; 10(5)2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-34062957

RESUMO

The α1-adrenoceptor agonist phenylephrine (PE) and Angiotensin II (Ang II) are both potent vasoconstrictors at peripheral resistance arteries. PE has pure vasoconstrictive properties. Ang II, additionally, modulates central nervous blood pressure (BP) control via sympathetic baroreflex resetting. However, it is unknown whether Ang II vs. PE mediated vasoconstriction at equipressor dose uniformly or specifically modifies arterial stiffness. We conducted a three-arm randomized placebo-controlled cross-over trial in 30 healthy volunteers (15 female) investigating the effects of Ang II compared to PE at equal systolic pressor dose on pulse wave velocity (PWV), pulse wave reflection (augmentation index normalized to heart rate 75/min, AIx) and non-invasive hemodynamics by Mobil-O-Graph™ and circulating core markers of endothelial (dys-)function. PE but not Ang II-mediated hypertension induced a strong reflex-decrease in cardiac output. Increases in PWV, AIx, total peripheral resistance and pulse pressure, in contrast, were stronger during PE compared to Ang II at equal mean aortic BP. This was accompanied by minute changes in circulating markers of endothelial function. Moreover, we observed differential hemodynamic changes after stopping either vasoactive infusion. Ang II- and PE-mediated BP increase specifically modifies arterial stiffness and hemodynamics with aftereffects lasting beyond mere vasoconstriction. This appears attributable in part to different interactions with central nervous BP control including modified baroreflex function.


Assuntos
Angiotensina II/farmacologia , Hemodinâmica/efeitos dos fármacos , Fenilefrina/farmacologia , Rigidez Vascular/efeitos dos fármacos , Vasoconstritores/farmacologia , Adulto , Barorreflexo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Masculino
13.
J Clin Hypertens (Greenwich) ; 23(7): 1363-1371, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34101968

RESUMO

Uncontrolled hypertension is a main risk factor for cardiovascular morbidity. Baroreflex activation therapy (BAT) is an effective therapy option addressing true resistant hypertension. We evaluated patients' eligibility for BAT in a staged assessment as well as adherence to antihypertensive drug therapy. Therefore, we analyzed files of 345 patients, attending the hypertension clinic at University Medicine Göttingen. Additionally, gas chromatographic-mass spectrometric urine analyses of selected individuals were performed evaluating their adherence. Most common cause for a revoked BAT recommendation was blood pressure (BP) control by drug adjustment (54.2%). Second leading cause was presence of secondary hypertension (31.6%). Patients to whom BAT was recommended (59 (17.1%)) were significantly more often male (67.8% vs. 43.3%, P = .0063), had a higher body mass index (31.8 ± 5.8 vs. 30.0 ± 5.7 kg/m², P = .0436), a higher systolic office (168.7 ± 24.7 vs. 147.7 ± 24.1 mmHg, P < .0001), and 24h ambulatory BP (155.0 ± 14.6 vs. 144.4 ± 16.8 mmHg, P = .0031), took more antihypertensive drugs (5.8 ± 1.3 vs. 4.4 ± 1.4, P < .0001), and suffered more often from numerous concomitant diseases. Eventually, 27 (7.8%) received a BAT system. In the toxicological analysis of 75 patients, mean adherence was 75.1%. 16 patients (21.3%) showed non-adherence. Thus, only a small number of patients eventually received a BAT system, as treatable reasons for apparently resistant hypertension could be identified frequently. This study is-to our knowledge-the first report of a staged assessment of patients' suitability for BAT and underlines the need for a careful examination and indication. Non-adherence was proven to be a relevant issue concerning apparently resistant hypertension and therefore non-eligibility for interventional antihypertensive therapy.


Assuntos
Barorreflexo , Hipertensão , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Adesão à Medicação
14.
Am J Physiol Regul Integr Comp Physiol ; 321(1): R62-R78, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33978481

RESUMO

Obese Zucker rats (OZRs) develop hypertension and hyperinsulinemia by 3 mo of age. Male OZRs also have diminished baroreflex-mediated activation of nucleus tractus solitarius (NTS) and bradycardia, which are improved by correcting their hyperglycemia. Conversely, 3-mo-old female OZRs and lean Zucker rats (LZRs) have equivalent baroreflex-mediated bradycardia that is impaired in 6-mo-old OZRs. We hypothesized that 3-mo-old female OZRs maintain NTS activation and baroreflexes coincident with glycemic control. We also hypothesized that 6-mo-old female OZRs develop impaired baroreflexes with hyperglycemia and diminished NTS activation. In 12- to 16-wk-old females, sympathetic nerve activity (SNA) and arterial pressure (AP) were higher in OZRs than LZRs. However, baroreflex-mediated inhibition of SNA and bradycardia were equivalent in female OZRs and LZRs. Unlike deficits in male OZRs, female OZRs and LZRs had no differences in phenylephrine-induced c-Fos expression in NTS or decreases in SNA and AP evoked by glutamate into NTS. Compared with hyperglycemia in male OZRs (217.9 ± 34.4 mg/dL), female OZRs had normal fed blood glucose levels (108.2 ± 1.6 mg/dL in LZRs and 113.6 ± 3.5 mg/dL in OZRs) with emerging glucose intolerance. Conscious 24- to 27-wk-old female OZRs had impaired baroreflex-mediated bradycardia, but fed blood glucose was modestly elevated (124.2 ± 5.2 mg/dL) and phenylephrine-induced c-Fos expression in NTS was comparable to LZRs. These data suggest that better glycemic control in 3-mo-old female OZRs prevents diminished NTS activation and baroreflexes, supporting the notion that hyperglycemia impairs these responses in male OZRs. However, 6-mo-old female OZRs had impaired baroreflex efficacy without diminished NTS activation or pronounced hyperglycemia, suggesting baroreflex deficits develop by different mechanisms in female and male OZRs.


Assuntos
Barorreflexo/fisiologia , Glicemia/metabolismo , Controle Glicêmico , Hipertensão , Obesidade , Envelhecimento , Animais , Colesterol/sangue , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperinsulinismo , Insulina/sangue , Masculino , Fenilefrina/farmacologia , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Zucker , Fatores Sexuais , Sistema Nervoso Simpático , Triglicerídeos/sangue
15.
Diabetes Res Clin Pract ; 177: 108793, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33951480

RESUMO

First-degree relatives of diabetes patients, despite being euglycemic, presented impaired BRS and exacerbation of sympathetic modulation after ingestion of a high fructose drink when challenged to orthostatic stress. This finding alerts the importance of early autonomic dysfunction even in clinically healthy people, especially in face of a stressful situation.


Assuntos
Diabetes Mellitus , Ingestão de Alimentos , Barorreflexo , Pressão Sanguínea , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/genética , Frutose/efeitos adversos , Frequência Cardíaca , Humanos , Reflexo
16.
Front Immunol ; 12: 637845, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995355

RESUMO

Baroreflex and chemoreflex act through the autonomic nervous system, which is involved with the neural regulation of inflammation. The present study reports the effects of reflex physiological sympathetic activation in endotoxemic rats using bilateral carotid occlusion (BCO), a physiological approach involving the baroreflex and chemoreflex mechanisms and the influence of the baroreceptors and peripheral chemoreceptors in the cardiovascular and systemic inflammatory responses. After lipopolysaccharide (LPS) administration, the arterial pressure was recorded during 360 min in unanesthetized rats, and serial blood samples were collected to analyze the plasma cytokine levels. BCO elicited the reflex activation of the sympathetic nervous system, providing the following outcomes: (I) increased the power of the low-frequency band in the spectrum of the systolic arterial pressure during the BCO period; (II) reduced the levels of pro-inflammatory cytokines in plasma, including the tumor necrosis factor (TNF) and the interleukin (IL)-1ß; (III) increased the plasma levels of anti-inflammatory cytokine IL-10, 90 min after LPS administration. Moreover, selective baroreceptor or chemoreceptor denervation deactivated mechanosensitive and chemical sensors, respectively, and decreased the release of the LPS-induced cytokine but did not alter the BCO modulatory effects. These results show, for the first time, that physiological reflex activation of the sympathetic circuit decreases the inflammatory response in endotoxemic rats and suggest a novel function for the baroreceptors as immunosensors during the systemic inflammation.


Assuntos
Barorreflexo/fisiologia , Endotoxemia/patologia , Inflamação/fisiopatologia , Pressorreceptores/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Sistema Nervoso Autônomo/fisiologia , Pressão Sanguínea/fisiologia , Células Quimiorreceptoras/fisiologia , Interleucina-10/sangue , Interleucina-1beta/sangue , Lipopolissacarídeos , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
17.
JACC Heart Fail ; 9(6): 430-438, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33992562

RESUMO

OBJECTIVES: The aim of this study was to assess sex differences in the efficacy and safety of baroreflex activation therapy (BAT) in the BeAT-HF (Baroreflex Activation Therapy for Heart Failure) trial. BACKGROUND: Patients were randomized 1:1 to receive guideline-directed medical therapy (GDMT) alone (control group) or BAT plus GDMT. METHODS: Pre-specified subgroup analyses including change from baseline to 6 months in 6-min walk distance (6MWD), quality of life (QoL) assessed using the Minnesota Living With Heart Failure Questionnaire (MLWHQ), New York Heart Association (NYHA) functional class, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were conducted in men versus women. RESULTS: Fifty-three women and 211 men were evaluated. Women had similar baseline NT-proBNP levels, 6MWDs, and percentage of subjects with NYHA functional class III symptoms but poorer MLWHQ scores (mean 62 ± 22 vs. 50 ± 24; p = 0.01) compared with men. Women experienced significant improvement from baseline to 6 months with BAT plus GDMT relative to GDMT alone in MLWHQ score (-34 ± 27 vs. -9 ± 23, respectively; p < 0.01), 6MWD (44 ± 45 m vs. -32 ± 118 m; p < 0.01), and improvement in NYHA functional class (70% vs. 27%; p < 0.01), similar to the responses seen in men, with no significant difference in safety. Women receiving BAT plus GDMT had a significant decrease in NT-proBNP (-43% vs. 7% with GDMT alone; difference -48%; p < 0.01), while in men this decrease was -15% versus 2%, respectively (difference -17%; p = 0.08), with an interaction p value of 0.05. CONCLUSIONS: Women in BeAT-HF had poorer baseline QoL than men but demonstrated similar improvements with BAT in 6MWD, QoL, and NYHA functional class. Women had a significant improvement in NT-proBNP, whereas men did not. (Baroreflex Activation Therapy for Heart Failure [BeAT-HF]; NCT02627196).


Assuntos
Terapia por Estimulação Elétrica , Insuficiência Cardíaca Sistólica , Insuficiência Cardíaca , Barorreflexo , Feminino , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca Sistólica/terapia , Humanos , Masculino , Peptídeo Natriurético Encefálico , Assistência Centrada no Paciente , Fragmentos de Peptídeos , Qualidade de Vida , Volume Sistólico
18.
Neurology ; 97(2): e136-e144, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-33947784

RESUMO

OBJECTIVE: To describe the natural history of afferent baroreflex failure (ABF) based on systematic review of clinical and laboratory data in patients with a diagnosis of ABF at Mayo Clinic Rochester. METHODS: We performed a retrospective chart review of all patients who underwent standardized autonomic reflex testing between 2000 and 2020 and had confirmation of the diagnosis of ABF by an autonomic disorders specialist. Patients were identified using a data repository of medical records. Variables included demographic, all-cause mortality, medications, ABF manifestations, comorbidities, and laboratory (autonomic testing, blood pressure monitoring, echocardiogram, brain imaging, plasma catecholamines, serum sodium level, and kidney function tests). RESULTS: A total of 104 patients with ABF were identified. Head and neck radiation was the most common etiology (86.5%), followed by neck surgery (5.8%) and other causes (7.7%). The most common findings were hypertension (87.5%), fluctuating blood pressure (78.8%), orthostatic hypotension (91.3%), syncope (58.6%), headache (22.1%), and tachycardia (20.2%). Patients commonly received antihypertensives (66.3%), pressor agents (41.3%), or a combination of both (19.2%). The median latency from completion of radiation to ABF was longer compared to the latency in the surgery group (p < 0.0001). Comorbidities, including complications from neck radiation, were frequently seen and all-cause mortality was 39.4% over a 20-year period. CONCLUSIONS: ABF should be suspected in patients with prior head and neck cancer treated by radiation or surgery who present with labile hypertension and orthostatic hypotension. Management may require both antihypertensive and pressor medications. The morbidity and mortality in ABF are high.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Barorreflexo/fisiologia , Vias Aferentes/fisiopatologia , Doenças do Sistema Nervoso Autônomo/complicações , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial , Humanos , Hipertensão/complicações , Estudos Retrospectivos
19.
Life Sci ; 278: 119534, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933461

RESUMO

Diabetes promotes renal sympathetic hyperactivity, autonomic imbalance, and cardiovascular and renal dysfunction. Bilateral renal denervation (BRD) has emerged as a treatment for diabetes; however, the mechanisms that underlie the beneficial effects of BRD are unknown. AIMS: The present study evaluated the effects of BRD on autonomic, cardiovascular, metabolic, and renal function in streptozotocin-diabetic rats. MAIN METHODS: Wistar rats were separated into three experimental groups: control (CTR), diabetic (DM), and diabetic that underwent BRD (DM BRD). BRD was performed two weeks after STZ-diabetes induction, the experiments were performed four weeks after DM induction. This study evaluated sympathetic vasomotor nerve activity in different territories (renal, lumbar and splanchnic), arterial baroreceptor reflex, metabolic and renal function. KEY FINDINGS: BRD significantly reduced glycemia, glycosuria, albuminuria, and SGLT2 gene expression in the kidney in DM rats. Renal sympathetic nerve activity (rSNA) was significantly increased and splanchnic sympathetic nerve activity (sSNA) was significantly decreased in DM rats, without changes in lumbar sympathetic nerve activity (lSNA). BRD was able to normalize sSNA and significantly increase lSNA in DM rats compared to control rats. Additionally, cardiac baroreceptor sensitivity was impaired in DM rats, and BRD significantly improved baroreflex sensitivity. SIGNIFICANCE: Our data suggest that renal nerves play an important role in autonomic, cardiovascular, and renal dysfunction in STZ-DM rats. Thus, sympathetic renal hyperactivity should be considered a possible therapeutic target in diabetic patients.


Assuntos
Sistema Cardiovascular , Denervação , Diabetes Mellitus Experimental/metabolismo , Rim/inervação , Rim/metabolismo , Animais , Barorreflexo , Pressão Sanguínea/efeitos dos fármacos , Cateterismo , Diabetes Mellitus Experimental/fisiopatologia , Coração , Frequência Cardíaca/efeitos dos fármacos , Hematócrito , Masculino , Pressorreceptores/fisiologia , Ratos , Ratos Wistar , Transportador 2 de Glucose-Sódio/metabolismo , Estreptozocina , Sistema Nervoso Simpático/efeitos dos fármacos
20.
Clin Neurophysiol ; 132(7): 1537-1542, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34023631

RESUMO

OBJECTIVE: Changes in baroreflex sensitivity have been reported in patients with idiopathic Parkinson's disease (PD). We sought to investigate the hypothesis that patients with isolated rapid eye movement (REM)-sleep behavior disorder (iRBD), known to be a prodromal stage for PD, will show abnormalities in baroreflex control. METHODS: Ten iRBD patients were compared to 10 sex- and age-matched healthy controls. Their cardiovascular parameters and muscle sympathetic nerve activity (MSNA) were evaluated at rest and during baroreflex stimulation. RESULTS: MSNA at rest was higher in iRBD patients (burst frequency [BF]: 44 ± 3 bursts/min; burst incidence [BI]: 60 ± 8 bursts/100 heartbeats) as compared to the controls (BF: 29 ± 3 bursts/min, p < 0.001; BI: 43 ± 9 bursts/100 heartbeats, p < 0.001). During baroreflex stimulation, iRBD patients showed increased absolute values of MSNA (BF: F = 62.728; p < 0.001; BI: F = 16.277; p < 0.001) as compared to the controls. The iRBD patients had decreased diastolic blood pressure at baseline and during lower body negative pressure, but the level of significance was not met. CONCLUSION: Our study shows increased MSNA and impaired baroreflex control in iRBD patients. We propose that the inhibitory effect of locus coeruleus on baroreflex function might be impaired, leading to the disinhibition of sympathetic outflow. SIGNIFICANCE: These findings might reflect the destruction of brain areas due to the ascending P-α-synuclein deposits in iRBD patients.


Assuntos
Fibras Adrenérgicas/fisiologia , Barorreflexo/fisiologia , Músculo Esquelético/inervação , Músculo Esquelético/fisiopatologia , Transtorno do Comportamento do Sono REM/diagnóstico , Transtorno do Comportamento do Sono REM/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos
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