RESUMEN
Microneurographic recordings of muscle sympathetic nerve activity (MSNA) reflect postganglionic sympathetic axonal activity directed toward the skeletal muscle vasculature. Recordings are typically evaluated for spontaneous bursts of MSNA; however, the filtering and integration of raw neurograms to obtain multiunit bursts conceals the underlying c-fiber discharge behavior. The continuous wavelet transform with matched mother wavelet has permitted the assessment of action potential discharge patterns, but this approach uses a mother wavelet optimized for an amplifier that is no longer commercially available (University of Iowa Bioengineering Nerve Traffic Analysis System; Iowa NTA). The aim of this project was to determine the morphology and action potential detection performance of mother wavelets created from the commercially available NeuroAmp (ADinstruments), from distinct laboratories, compared with a mother wavelet generated from the Iowa NTA. Four optimized mother wavelets were generated in a two-phase iterative process from independent datasets, collected by separate laboratories (one Iowa NTA, three NeuroAmp). Action potential extraction performance of each mother wavelet was compared for each of the NeuroAmp-based datasets. The total number of detected action potentials was not significantly different across wavelets. However, the predictive value of action potential detection was reduced when the Iowa NTA wavelet was used to detect action potentials in NeuroAmp data, but not different across NeuroAmp wavelets. To standardize approaches, we recommend a NeuroAmp-optimized mother wavelet be used for the evaluation of sympathetic action potential discharge behavior when microneurographic data are collected with this system.NEW & NOTEWORTHY The morphology of custom mother wavelets produced across laboratories using the NeuroAmp was highly similar, but distinct from the University of Iowa Bioengineering Nerve Traffic Analysis System. Although the number of action potentials detected was similar between collection systems and mother wavelets, the predictive value differed. Our data suggest action potential analysis using the continuous wavelet transform requires a mother wavelet optimized for the collection system.
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Potenciales de Acción , Análisis de Ondículas , Potenciales de Acción/fisiología , Animales , Sistema Nervioso Simpático/fisiología , Músculo Esquelético/fisiología , MasculinoRESUMEN
Pre-clinical models indicate that Amiloride (AMD) reduces baroreflex sensitivity and perturbs homeostatic blood pressure (BP) regulation. However, it remains unclear whether these findings translate to humans. This study investigated whether oral administration of AMD reduces spontaneous cardiac and sympathetic baroreflex sensitivity and perturbs BP regulation in healthy young humans. Heart rate (HR; electrocardiography), beat-to-beat BP (photoplethysmography), and muscle sympathetic activity (MSNA, microneurography) were continuously measured in 10 young subjects (4 females) during rest across two randomized experimental visits: (1) after 3 hours of oral administration of placebo (PLA - 10 mg of methylcellulose within a gelatin capsule) and (2) after 3 hours of oral administration of AMD (10 mg). Visits were separated for at least 48 hours. We calculated the standard deviation and other indices of BP variability. Spontaneous cardiac baroreflex was assessed via the sequence technique and cardiac autonomic modulation through time- and frequency-domain HR variability. The sensitivity (gain) of the sympathetic baroreflex was determined via weighted linear regression analysis between MSNA and diastolic BP. AMD did not affect HR, BP, and MSNA compared to PLA. Indexes of cardiac autonomic modulation (time- and frequency-domain HR variability) and BP variability were also unchanged after AMD ingestion. Likewise, AMD did not modify the gain of both spontaneous cardiac and sympathetic arterial baroreflex. A single oral dose of AMD does not affect spontaneous arterial baroreflex sensitivity and BP variability in healthy young adults.
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BACKGROUND: Physiology is widely recognized as a difficult course, which can potentially increase students' withdrawal and failures rates. Several factors are likely contributing to the difficulties in learning physiology, including inherent features of the discipline as well as aspects related to instructions and/or students' perception. With regards to the later, it is currently unknown how students of exercise physiology think and explain physiology in terms of its cause or consequence (i.e., teleological or mechanistic thinking). Therefore, the aims of the present study were to determine 1) whether undergraduate students' perception of cardiorespiratory physiology during exercise follows a predominant teleological or mechanistic thinking, and 2) whether prior enrollment in physiology courses can influence the predominance of teleological vs. mechanistic thinking. METHODS: The test instrument was an online questionnaire about exercise physiology consisting of nine incomplete sentences about exercise physiology where students had to choose between a teleological or a mechanistic complement. The questionnaire was administered to undergraduate students in the following areas: 1) Movement Sciences (n = 152), 2) Health-related (n = 81) and, 3) Health-unrelated programs (n = 64). Students in Movement Sciences and Health-related programs were also analyzed separately in the following categories: 1) students who previously undertook physiology courses, and 2) students who did not take physiology courses. RESULTS: Overall, all groups presented a percentage of teleological thinking above 58%, which is considerably high. Teleological thinking was significantly higher in health-unrelated programs than health-related and movement sciences programs (76 ± 16% vs. 58 ± 26% vs. 61 ± 25%; P < 0.01). Further, students with prior enrollment in physiology classes presented a significantly lower percentage of teleological thinking than students without physiology classes (59 ± 25% vs. 72 ± 22%, respectively; P < 0.01), but the overall teleological reasoning remained predominant. CONCLUSIONS: These results confirm the hypothesis that undergraduate students tend to present teleological as opposed to mechanistic thinking in exercise physiology. Furthermore, although undergraduate students with prior enrollment in physiology classes presented significantly lower teleological thinking, it remained highly predominant suggesting that teleological thinking is partially independent of the degree of familiarity with this discipline.
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Fisiología , Estudiantes , Humanos , Aprendizaje , Solución de Problemas , Percepción , Fisiología/educaciónRESUMEN
The purpose of this study was to determine whether there are sex differences in the cardiorespiratory and sympathetic neurocirculatory responses to central, peripheral, and combined central and peripheral chemoreflex activation. Ten women (29 ± 6 years, 22.8 ± 2.4 kg/m2 : mean ± SD) and 10 men (30 ± 7 years, 24.8 ± 3.2 kg/m2 ) undertook randomized 5 min breathing trials of: room air (eucapnia), isocapnic hypoxia (10% oxygen (O2 ); peripheral chemoreflex activation), hypercapnic hyperoxia (7% carbon dioxide (CO2 ), 50% O2 ; central chemoreflex activation) and hypercapnic hypoxia (7% CO2 , 10% O2 ; central and peripheral chemoreflex activation). Control trials of isocapnic hyperoxia (peripheral chemoreflex inhibition) and hypocapnic hyperoxia (central and peripheral chemoreflex inhibition) were also included. Muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; finger photoplethysmography) and minute ventilation ( VÌ$\dot{\rm{V}}$E ; pneumotachometer) were measured. Total MSNA (P = 1.000 and P = 0.616), MAP (P = 0.265) and VÌ$\dot{\rm{V}}$E (P = 0.587 and P = 0.472) were not different in men and women during eucapnia and during isocapnic hypoxia. Women exhibited attenuated increases in VÌ$\dot{\rm{V}}$E during hypercapnic hyperoxia (27.3 ± 6.3 vs. 39.5 ± 7.5 l/min, P < 0.0001) and hypercapnic hypoxia (40.9 ± 9.1 vs. 53.8 ± 13.3 l/min, P < 0.0001) compared with men. However, total MSNA responses were augmented in women (hypercapnic hyperoxia 378 ± 215 vs. 258 ± 107%, P = 0.017; hypercapnic hypoxia 607 ± 290 vs. 362 ± 268%, P < 0.0001). No sex differences in total MSNA, MAP or VÌ$\dot{\rm{V}}$E were observed during isocapnic hyperoxia and hypocapnic hyperoxia. Our results indicate that young women have augmented sympathetic responses to central chemoreflex activation, which explains the augmented MSNA response to combined central and peripheral chemoreflex activation. KEY POINTS: Sex differences in the control of breathing have been well studied, but whether there are differences in the sympathetic neurocirculatory responses to chemoreflex activation between healthy women and men is incompletely understood. We observed that, compared with young men, young women displayed augmented increases in muscle sympathetic nerve activity during both hypercapnic hyperoxia (central chemoreflex activation) and hypercapnic hypoxia (central and peripheral chemoreflex activation) but had attenuated increases in minute ventilation. In contrast, no sex differences were found in either muscle sympathetic nerve activity or minute ventilation responses to isocapnic hypoxia (peripheral chemoreceptor stimulation). Young women have blunted ventilator, but augmented sympathetic responses, to central (hypercapnic hyperoxia) and combined central and peripheral chemoreflex activation (hypercapnic hypoxia), compared with young men. The possible causative association between the reduced ventilation and heightened sympathetic responses in young women awaits validation.
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Hiperoxia , Adulto , Presión Sanguínea , Dióxido de Carbono , Células Quimiorreceptoras/fisiología , Femenino , Humanos , Hipercapnia , Hipoxia , Masculino , Oxígeno , Caracteres Sexuales , Sistema Nervioso Simpático/fisiología , Adulto JovenRESUMEN
Resting beat-to-beat blood pressure variability is a powerful predictor of cardiovascular events and end-organ damage. However, its underlying mechanisms remain unknown. Herein, we tested the hypothesis that a potentiation of GABAergic synaptic transmission by diazepam would acutely increase resting beat-to-beat blood pressure variability. In 40 (17 females) young, normotensive subjects, resting beat-to-beat blood pressure (finger photoplethysmography) was continuously measured for 5-10 min, 60 min after the oral administration of either diazepam (10 mg) or placebo. The experiments were conducted in a randomized, double-blinded, and placebo-controlled design. Stroke volume was estimated from the blood pressure waveform (ModelFlow) permitting the calculation of cardiac output and total peripheral resistance. Direct recordings of muscle sympathetic nerve activity (MSNA, microneurography) were obtained in a subset of subjects (n = 13), and spontaneous cardiac and sympathetic baroreflex sensitivity were calculated. Compared with placebo, diazepam significantly increased the standard deviation of systolic blood pressure (4.7 ± 1.4 vs. 5.7 ± 1.5 mmHg, P = 0.001), diastolic blood pressure (3.8 ± 1.2 vs. 4.5 ± 1.2 mmHg, P = 0.007), and mean blood pressure (3.8 ± 1.1 vs. 4.5 ± 1.1 mmHg, P = 0.002), as well as cardiac output (469 ± 149 vs. 626 ± 259 mL/min, P < 0.001) and total peripheral resistance (1.0 ± 0.3 vs. 1.4 ± 0.6 mmHg/L/min, P < 0.001). Similar results were found using different indices of variability. Furthermore, diazepam reduced MSNA (placebo: 22 ± 6 vs. diazepam: 18 ± 8 bursts/min, P = 0.025) without affecting the arterial baroreflex control of heart rate (placebo: 18.6 ± 6.7 vs. diazepam: 18.8 ± 7.0 ms/mmHg, P = 0.87) and MSNA (placebo: -3.6 ± 1.2 vs. diazepam: -3.4 ± 1.5 bursts/100 Hb/mmHg, P = 0.55). Importantly, these findings were not impacted by biological sex. We conclude that GABAA receptors modulate resting beat-to-beat blood pressure variability in young adults.
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Barorreflejo , Diazepam , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Diazepam/farmacología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Músculo Esquelético/fisiología , Receptores de GABA-A , Sistema Nervioso Simpático/fisiología , Transmisión Sináptica , Adulto JovenRESUMEN
The exercise pressor reflex is a feedback mechanism engaged upon stimulation of mechano- and metabosensitive skeletal muscle afferents. Activation of these afferents elicits a reflex increase in heart rate, blood pressure, and ventilation in an intensity-dependent manner. Consequently, the exercise pressor reflex has been postulated to be one of the principal mediators of the cardiorespiratory responses to exercise. In this updated review, we will discuss classical and recent advancements in our understating of the exercise pressor reflex function in both human and animal models. Particular attention will be paid to the afferent mechanisms and pathways involved during its activation, its effects on different target organs, its potential role in the abnormal cardiovascular response to exercise in diseased states, and the impact of age and biological sex on these responses. Finally, we will highlight some unanswered questions in the literature that may inspire future investigations in the field.
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Sistema Cardiovascular , Reflejo , Animales , Presión Sanguínea/fisiología , Ejercicio Físico/fisiología , Humanos , Contracción Muscular/fisiología , Músculo Esquelético/fisiología , Reflejo/fisiologíaRESUMEN
The incidence of Parkinson's disease (PD) is increasing worldwide. Although the PD hallmark is the motor impairments, nonmotor dysfunctions are now becoming more recognized. Recently, studies have suggested that baroreflex dysfunction is one of the underlying mechanisms of cardiovascular dysregulation observed in patients with PD. However, the large body of literature on baroreflex function in PD is unclear. The baroreflex system plays a major role in the autonomic, and ultimately blood pressure and heart rate, adjustments that accompany acute cardiovascular stressors on a daily basis. Therefore, impaired baroreflex function (i.e., decreased sensitivity or gain) can lead to altered neural cardiovascular responses. Since PD affects parasympathetic and sympathetic branches of the autonomic nervous system and both are orchestrated by the baroreflex system, understanding of this crucial mechanism in PD is necessary. In the present review, we summarize the potential altered central and peripheral mechanisms affecting the feedback-controlled loops that comprise the reflex arc in patients with PD. Major factors including arterial stiffness, reduced number of C1 and activation of non-C1 neurons, presence of central α-synuclein aggregation, cardiac sympathetic denervation, attenuated muscle sympathetic nerve activity, and lower norepinephrine release could compromise baroreflex function in PD. Results from patients with PD and from animal models of PD provide the reader with a clearer picture of baroreflex function in this clinical condition. By doing so, our intent is to stimulate future studies to evaluate several unanswered questions in this research area.
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Barorreflejo/fisiología , Presión Sanguínea/fisiología , Bulbo Raquídeo/fisiopatología , Enfermedad de Parkinson/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Animales , Humanos , Bulbo Raquídeo/metabolismo , Bulbo Raquídeo/patologíaRESUMEN
Signal-averaged sympathetic transduction of blood pressure (BP) is inversely related to resting muscle sympathetic nerve activity (MSNA) burst frequency in healthy cohorts. Whether this represents a physiological compensatory adaptation or a methodological limitation, remains unclear. The current analysis aimed to determine the contribution of methodological limitations by evaluating the dependency of MSNA transduction at different levels of absolute BP. Thirty-six healthy participants (27 ± 7 yr, 9 females) underwent resting measures of beat-to-beat heart rate, BP, and muscle sympathetic nerve activity (MSNA). Tertiles of mean arterial pressure (MAP) were computed for each participant to identify cardiac cycles occurring below, around, and above the MAP operating pressure (OP). Changes in hemodynamic variables were computed across 15 cardiac cycles within each MAP tertile to quantify sympathetic transduction. MAP increased irrespective of sympathetic activity when initiated below the OP, but with MSNA bursts provoking larger rises (3.0 ± 0.9 vs. 2.1 ± 0.7 mmHg; P < 0.01). MAP decreased irrespective of sympathetic activity when initiated above the OP, but with MSNA bursts attenuating the drop (-1.3 ± 1.1 vs. -3.1 ± 1.2 mmHg; P < 0.01). In participants with low versus high resting MSNA (12 ± 4 vs. 32 ± 10 bursts/min), sympathetic transduction of MAP was not different when initiated by bursts below (3.2 ± 1.0 vs. 2.8 ± 0.9 mmHg; P = 0.26) and above the OP (-1.0 ± 1.3 vs. -1.6 ± 0.8 mmHg; P = 0.08); however, low resting MSNA was associated with a smaller proportion of MSNA bursts firing above the OP (15 ± 5 vs. 22 ± 5%; P < 0.01). The present analyses demonstrate that the signal-averaging technique for calculating sympathetic transduction of BP is influenced by the timing of an MSNA burst relative to cyclic oscillations in BP.NEW & NOTEWORTHY The current signal-averaging technique for calculating sympathetic transduction of blood pressure does not consider the arterial pressure at which each muscle sympathetic burst occurs. A burst firing when mean arterial pressure is above the operating pressure was associated with a decrease in blood pressure. Thus, individuals with higher muscle sympathetic nerve activity demonstrate a reduced sympathetic transduction owing to the weighted contribution of more sympathetic bursts at higher levels of arterial pressure.
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Presión Arterial , Sistema Cardiovascular/inervación , Músculo Esquelético/inervación , Descanso , Sistema Nervioso Simpático/fisiología , Adulto , Determinación de la Presión Sanguínea , Impedancia Eléctrica , Electrodiagnóstico , Femenino , Humanos , Masculino , Fotopletismografía , Factores de Tiempo , Adulto JovenRESUMEN
Calculating the blood pressure (BP) response to a burst of muscle sympathetic nerve activity (MSNA), termed sympathetic transduction, may be influenced by an individual's resting burst frequency. We examined the relationships between sympathetic transduction and MSNA in 107 healthy males and females and developed a normalized sympathetic transduction metric to incorporate resting MSNA. Burst-triggered signal averaging was used to calculate the peak diastolic BP response following each MSNA burst (sympathetic transduction of BP) and following incorporation of MSNA burst cluster patterns and amplitudes (sympathetic transduction slope). MSNA burst frequency was negatively correlated with sympathetic transduction of BP (r = -0.42; P < 0.01) and the sympathetic transduction slope (r = -0.66; P < 0.01), independent of sex. MSNA burst amplitude was unrelated to sympathetic transduction of BP in males (r = 0.04; P = 0.78), but positively correlated in females (r = 0.44; P < 0.01) and with the sympathetic transduction slope in all participants (r = 0.42; P < 0.01). To control for MSNA, the linear regression slope of the log-log relationship between sympathetic transduction and MSNA burst frequency was used as a correction exponent. In subanalysis of males (38 ± 10 vs. 14 ± 4 bursts/min) and females (28 ± 5 vs. 12 ± 4 bursts/min) with high versus low MSNA, sympathetic transduction of BP and sympathetic transduction slope were lower in participants with high MSNA (all P < 0.05). In contrast, normalized sympathetic transduction of BP and normalized sympathetic transduction slope were similar in males and females with high versus low MSNA (all P > 0.22). We propose that incorporating MSNA burst frequency into the calculation of sympathetic transduction will allow comparisons between participants with varying levels of resting MSNA.
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Potenciales de Acción , Presión Sanguínea , Sistema Cardiovascular/inervación , Electromiografía , Músculo Esquelético/inervación , Procesamiento de Señales Asistido por Computador , Sistema Nervioso Simpático/fisiología , Adolescente , Adulto , Determinación de la Presión Sanguínea , Electrocardiografía , Femenino , Voluntarios Sanos , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Prueba de Estudio Conceptual , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Isometric handgrip training (IHT) promotes vascular adaptations in different populations. AIMS: We assessed the sex differences in vascular adaptations of IHT in a sample of older adults with symptomatic peripheral artery disease (PAD). METHODS: Fifty-three older patients with symptomatic PAD (6 women and 13 men in IHT and 13 women and 21 men in the control group) participated in this study. The IHT group performed 3 sessions per week, for 8 weeks, consisting of 4 sets of isometric contractions for 2 min at 30% of maximum voluntary contraction and a 4-min interval between sets. The control group received a compression ball in order to minimize the placebo effects, representing sham training. Blood flow and brachial flow-mediated dilation were analyzed at before and after 8 weeks of intervention. We compared the responses (Δ = post-pre values) of each group (women control, women IHT, men control, and men IHT) with a Kruskal-Wallis test. RESULTS: There were no differences in all groups after 8 weeks of IHT in Δ brachial diameter (p = 0.850), Δ flow-mediated dilation (p = 0.241), Δ time to peak diameter (p = 0.528), and Δ FMD/AUC (p = 0.397). CONCLUSIONS: There are no effects of sex on vascular adaptation after 8 weeks of IHT in older adults with symptomatic PAD.
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Arteria Braquial/fisiopatología , Terapia por Ejercicio , Fuerza de la Mano , Contracción Isométrica , Enfermedad Arterial Periférica/terapia , Vasodilatación , Adaptación Fisiológica , Factores de Edad , Anciano , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Flujo Sanguíneo Regional , Estudios Retrospectivos , Factores Sexuales , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The mechanisms underlying functional impairments in symptomatic PAD patients are controversial and poorly understood. Endothelial dysfunction and arterial stiffness have been proposed as potential mechanisms related to functional impairment in symptomatic PAD patients, however, more studies are needed to confirm these associations. OBJECTIVE: To analyze the association between vascular function and walking impairment in patients with peripheral arterial disease (PAD) and symptoms of claudication. METHODS: This was a cross-sectional study that included 68 patients with symptomatic PAD. All patients underwent an objective (Six-minute walk test [6MWT], 4-meter walk test) and a subjective (Walking Impairment Questionnaire [WIQ]) measurement of walking impairment. Vascular parameters measured were pulse-wave velocity (PWV) and flow-mediated dilation (FMD). Multiple linear regression was performed to investigate the association among walking impairment variables with vascular function parameters. RESULTS: No significant associations between the claudication onset distance (PWV: b=.060, P = 0.842; FMD: b=-.192, P = 0.456), 6MWT (PWV: b=.007, P = 0..975; FMD: b=.090, P = 0.725), WIQ distance (PWV: b=.337, P = 0.117; FMD: b=-.025, P = 0.895) WIQ speed (PWV: b=.320, P = 0.181; FMD: b=-.028, P = 0.497), WIQ stairs (PWV: b=.256, P = 0.204; FMD: b=-.228, P = 0.230), 4-meter usual walk (PWV: b=-.421, P = 0.107; FMD: b=-.338, P = 0.112), 4-meter fast walk (PWV: b=-.496, P = 0.063; FMD: b=-.371, P = 0.086) and vascular function were found. CONCLUSIONS: In symptomatic PAD patients, vascular function is not associated to walking impairment, even when adjusting for comorbid conditions and diabetes.
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Endotelio Vascular/fisiopatología , Claudicación Intermitente/fisiopatología , Enfermedad Arterial Periférica/fisiopatología , Rigidez Vascular , Vasodilatación , Caminata , Anciano , Comorbilidad , Estudios Transversales , Tolerancia al Ejercicio , Femenino , Humanos , Claudicación Intermitente/diagnóstico , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico , Valor Predictivo de las Pruebas , Análisis de la Onda del Pulso , Encuestas y Cuestionarios , Prueba de PasoRESUMEN
We investigated the acute effects of isometric biceps exercise on resting and ambulatory blood pressure in hypertensive adults. A total of 12 medicated hypertensive adults (aged 47±7 years; body mass index 27.2±2.7 kg/m2; resting blood pressure 123±12/74±6 mmHg) performed an isometric biceps exercise session (bilateral biceps exercise; 4×1 min at 30% of 1-RM, 2 min recovery) and a control session (without exercise) in a randomized order separated by a 7 to 10-day period. Resting blood pressure, heart rate, and heart rate variability indexes (SDNN, RMSSD, LF, HF, and LF/HF) were measured pre- and up to 30 min post-sessions. Next, ambulatory blood pressure was monitored during 22-hour post-sessions (awake and asleep periods). No significant changes were observed for resting blood pressure, heart rate, or heart rate variability indexes up to 30 min post-sessions (p>0.05). Furthermore, no significant differences were observed in average ambulatory blood pressure values in 22-hour (126±11/71±6 mmHg vs. 126±15/71±9 mmHg), awake (127±10/74±6 mmHg vs. 130±14/75±10 mmHg), and asleep (123±15/68±6 mmHg vs. 120±17/66±9 mmHg) periods between the control and isometric sessions, respectively (p>0.05). In conclusion, an isometric biceps exercise session does not elicit an acute antihypertensive effect in adults with hypertension, which suggests that its prescription to improve the acute BP control is limited.
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Presión Sanguínea , Ejercicio Físico/fisiología , Hipertensión , Músculo Esquelético/fisiología , Adulto , Monitoreo Ambulatorio de la Presión Arterial , Estudios Cruzados , Terapia por Ejercicio , Femenino , Frecuencia Cardíaca , Humanos , Contracción Isométrica , Masculino , Persona de Mediana EdadRESUMEN
Nonmotor symptoms are common in Parkinson's disease (PD) and they include dysregulation of cardiovascular system, which adversely affects quality of life. Recent studies provide indirect evidence that baroreflex dysfunction may be one of the mechanisms of cardiovascular dysregulation in PD. Herein, we tested the hypothesis that the baroreflex gain, assessed across an extensive range of the reflex arc by eliciting rapid changes in blood pressure (BP) induced by sequential boluses of vasoactive drugs (modified-Oxford technique) would be attenuated in middle-aged patients with PD. Beat-to-beat heart rate (electrocardiography) and BP (finger photoplethysmography) were obtained during 10 min of supine rest preceding the modified-Oxford (bolus of nitroprusside followed by phenylephrine 1 min afterward) in 11 patients with PD (51 ± 6 yr) and 7 age-matched controls (47 ± 6 yr). The resulting systolic BP and R-R interval responses were plotted and fitted with segmental linear regression and symmetric sigmoid model. Spontaneous indices obtained via sequence technique were also used to estimate baroreflex gain. Compared with controls, the estimated gains measured by segmental linear regression (patients: 3.83 ± 2.6 ms/mmHg versus controls: 7.78 ± 1.7 ms/mmHg; P = 0.003) and symmetric sigmoid model (patients: 12.36 ± 6.9 ms/mmHg versus controls: 32.02 ± 19.0 ms/mmHg; P = 0.009) were lower in patients with PD. The operating range of BP was larger in patients with PD compared with controls (13 ± 7 mmHg versus controls: 7 ± 3 mmHg; P = 0.032). Of note, the gain obtained from spontaneous indices was similar between groups. These data indicate that baroreflex gain was reduced by >50% in PD, thereby providing clear and direct evidence that cardiovagal baroreflex dysfunction occurs in PD.NEW & NOTEWORTHY Attenuated baroreflex gain may contribute to adverse cardiovascular outcomes, including orthostatic intolerance symptoms typically observed in patients with Parkinson's disease. We found that the baroreflex gain (assessed by the modified-Oxford technique) is attenuated and accompanied by an increased operating range in patients with Parkinson's disease. These findings highlight that cardiovascular perturbations are required to detect baroreflex impairments and that spontaneous indices do not reveal cardiovagal-baroreflex dysfunction in a middle-aged group of patients with Parkinson's disease.
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Barorreflejo , Enfermedad de Parkinson/fisiopatología , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitroprusiato/farmacología , Fenilefrina/farmacología , Vasoconstrictores/farmacología , Vasodilatadores/farmacologíaRESUMEN
Cerebral blood flow is tightly coupled with local neuronal activation and metabolism, i.e., neurovascular coupling (NVC). Studies suggest a role of sympathetic nervous system in the regulation of cerebral blood flow. However, this is controversial, and the sympathetic regulation of NVC in humans remains unclear. Since impaired NVC has been identified in several chronic diseases associated with a heightened sympathetic activity, we aimed to determine whether reflex-mediated sympathetic activation via lower body negative pressure (LBNP) attenuates NVC in humans. NVC was assessed using a visual stimulation protocol (5 cycles of 30 s eyes closed and 30 s of reading) in 11 healthy participants (aged 24 ± 3 yr). NVC assessments were made under control conditions and during LBNP at -20 and -40 mmHg. Posterior (PCA) and middle (MCA) cerebral artery mean blood velocity (Vmean) and vertebral artery blood flow (VAflow) were simultaneously determined with cardiorespiratory variables. Under control conditions, the visual stimulation evoked a robust increase in PCAVmean (∆18.0 ± 4.5%), a moderate rise in VAflow (∆9.6 ± 4.3%), and a modest increase in MCAVmean (∆3.0 ± 1.9%). The magnitude of NVC response was not affected by mild-to-moderate LBNP (all P > 0.05 for repeated-measures ANOVA). Given the small change that occurred in partial pressure of end-tidal CO2 during LBNP, this hypocapnia condition was matched via voluntary hyperventilation in absence of LBNP in a subgroup of participants (n = 8). The mild hypocapnia during LBNP did not exert a confounding influence on the NVC response. These findings indicate that the NVC is not influenced by LBNP or mild hypocapnia in humans.NEW & NOTEWORTHY Visual stimulation evoked a robust increase in posterior cerebral artery velocity and a modest increase in vertebral artery blood flow, i.e., neurovascular coupling (NVC), which was unaffected by lower body negative pressure (LBNP) in humans. In addition, although LBNP induced a mild hypocapnia, this degree of hypocapnia in the absence of LBNP failed to modify the NVC response.
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Arterias Cerebrales/fisiología , Hemodinámica , Presión Negativa de la Región Corporal Inferior/efectos adversos , Sistema Nervioso Simpático/fisiología , Adulto , Dióxido de Carbono/sangre , Circulación Cerebrovascular , Femenino , Humanos , Presión Negativa de la Región Corporal Inferior/métodos , Masculino , Estimulación Luminosa , ReflejoRESUMEN
The arterial baroreflex has dominant control over multiunit muscle sympathetic nerve activity (MSNA) burst occurrence, but whether this extends to all single units or is influenced by resting blood pressure status is unclear. In 22 men (32 ± 8 yr), we assessed 68 MSNA single units during sequential bolus injections of nitroprusside and phenylephrine (modified Oxford). Sympathetic baroreflex sensitivity (sBRS) was quantified as the weighted negative linear regression slope between diastolic blood pressure (DBP) and single-unit spike firing probability and multiple spike firing. Strong negative linear relationships (r ≥ -0.50) between DBP and spike firing probability were observed in 63/68 (93%) single units (-2.27 ± 1.27%·cardiac cycle-1·mmHg-1 [operating range, 18 ± 8 mmHg]). In contrast, only 45/68 (66%) single units had strong DBP-multiple spike firing relationships (-0.13 ± 0.18 spikes·cardiac cycle-1·mmHg-1 [operating range, 14 ± 7 mmHg]). Participants with higher resting DBP (65 ± 3 vs. 77 ± 3 mmHg, P < 0.001) had similar spike firing probability sBRS (low vs. high, -2.08 ± 1.08 vs. -2.46 ± 1.42%·cardiac cycle-1·mmHg-1, P = 0.33), but a smaller sBRS operating range (20 ± 6 vs. 16 ± 9 mmHg, P = 0.01; 86 ± 24 vs. 52 ± 25% of total range, P < 0.001) and a higher proportion of single units without arterial baroreflex control outside this range [6/31 (19%) vs. 21/32 (66%), P < 0.001]. Participants with higher resting DBP also had fewer single units with arterial baroreflex control of multiple spike firing (79 vs. 53%, P = 0.04). The majority of MSNA single units demonstrate strong arterial baroreflex control over spike firing probability during pharmacological manipulation of blood pressure. Changes in single-unit sBRS operating range and control of multiple spike firing may represent altered sympathetic recruitment patterns associated with the early development of hypertension.NEW & NOTEWORTHY Muscle sympathetic single units can be differentially controlled during stress. In contrast, we demonstrate that 93% of single units maintain strong arterial baroreflex control during pharmacological manipulation of blood pressure. Interestingly, the operating range and proportion of single units that lose arterial baroreflex control outside of this range are influenced by resting blood pressure levels. Altered single unit, but not multiunit, arterial baroreflex control may represent changes in sympathetic recruitment patterns in early stage development of hypertension.
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Arterias/fisiología , Barorreflejo , Presión Sanguínea , Músculo Liso Vascular/fisiología , Sistema Nervioso Simpático/fisiología , Adulto , Arterias/efectos de los fármacos , Humanos , Masculino , Conducción Nerviosa , Nitroprusiato/farmacología , Fenilefrina/farmacología , Vasodilatadores/farmacologíaRESUMEN
Fluctuations in diastolic pressure modulate muscle sympathetic nerve activity (MSNA) through the arterial baroreflex. A higher sympathetic baroreflex sensitivity (sBRS) to pressure falls compared with rises has been reported; however, the underlying mechanisms are unclear. We assessed whether beat-to-beat falling and rising diastolic pressures operate on two distinct baroreflex response curves. Twenty-two men (32 ± 8 yr) underwent sequential bolus injections of nitroprusside and phenylephrine (modified Oxford test) with continuous recording of heart rate, blood pressure, and MSNA. The weighted negative linear regression slope between falling or rising diastolic pressure and MSNA burst incidence quantified sBRSfall and sBRSrise, respectively. The diastolic pressure evoking a MSNA burst incidence of 50 (T50) was calculated. sBRSfall was greater than sBRSrise (-6.24 ± 2.80 vs. -4.34 ± 2.16 bursts·100 heartbeats-1·mmHg-1, P = 0.01) and had a narrower operating range (14 ± 8 vs. 20 ± 10 mmHg, P = 0.01) that was shifted rightward (T50, 75 ± 9 and 70 ± 11 mmHg, P < 0.001). At diastolic pressures below baseline, sBRSfall was less than sBRSrise (-1.81 ± 1.31 vs. -3.59 ± 1.70 bursts·100 heartbeats-1·mmHg-1, P = 0.003) as low absolute pressures operated closer to the saturation plateau on the falling, compared with the rising pressure curve. At pressures above baseline, sBRSfall was greater than sBRSrise (-5.23 ± 1.94 and -3.79 ± 1.67 bursts·100 heartbeats-1·mmHg-1, P = 0.03). These findings demonstrate that the sympathetic arterial baroreflex possesses two response curves for processing beat-to-beat diastolic pressure falls and rises. The falling pressure curve is rightward shifted, which reduces sensitivity to falling pressure at low absolute pressures. This demonstrates that the direction of the hysteresis is influenced by the prevailing pressure level relative to each baroreflex response curve.NEW & NOTEWORTHY The findings show that the arterial baroreflex processes diastolic pressure dependent on the direction of pressure change from the previous beat, yielding two distinct baroreflex response curves to falling and rising pressure. Overall, the falling pressure curve is rightward shifted and more sensitive. The rightward shift caused a hysteresis reversal at hypotensive pressures as the falling pressure saturation plateau of the sigmoid response curve occurred at higher pressures than the rising pressure curve.
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Presión Arterial , Barorreflejo , Frecuencia Cardíaca , Músculo Esquelético/inervación , Nervio Peroneo/fisiología , Sistema Nervioso Simpático/fisiología , Adulto , Presión Arterial/efectos de los fármacos , Barorreflejo/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Factores de Tiempo , Vasoconstrictores/farmacología , Vasodilatadores/farmacologíaRESUMEN
NEW FINDINGS: What is the central question of this study? Delayed cardiovascular responses occur following a single bout of remote ischaemic preconditioning (RIPC). Is heart rate variability (HRV), a surrogate marker of cardiac vagal control, able to detect a delayed effect after a single bout of RIPC? Do repeated bouts of RIPC further alter HRV? What is the main finding and its importance? Indices of HRV indicated a shift in sympathovagal balance toward greater parasympathetic activity following 2 weeks of RIPC but not after a single bout of RIPC. Thus, repeated bouts of RIPC were necessary to elicit changes in autonomic function. ABSTRACT: Remote ischaemic preconditioning (RIPC), induced by brief periods of ischaemia followed by reperfusion, protects against ischaemia-reperfusion injury and improves microvascular function. However, the effect of RIPC on autonomic function remains unclear. We hypothesized that RIPC, administered as a single bout or repeated over a 2-week period, will increase markers of cardiac vagal control measured by heart rate variability (HRV). Thirty-two young adults performed a single bout (n = 13), repeated bouts (n = 11), or served as a time control (n = 8). RIPC sessions consisted of four repetitions of 5 min unilateral brachial artery occlusion interspersed by 5 min of reperfusion. For the single bout protocol, resting lead II electrocardiogram (ECG) was collected before and 24, 48, 72 and 168 h post-RIPC. The repeated bout protocol consisted of three 4-day periods of RIPC training, each interspersed by a 1-day break. Similar to time controls, ECG was collected before and 24 h after the last RIPC bout. HRV was analysed by power spectral density and symbolic dynamics using 350-beat ECG segments. After a single bout of RIPC, no changes in HRV were observed at any time point (P > 0.05). After 2 weeks of repeated RIPC, the percentage of zero-variation fragments (baseline = 13.1 ± 1.9%, post-RIPC = 6.9 ± 1.5%, P < 0.05) and the LF/HF ratio decreased (baseline = 1.1 ± 0.2, post-RIPC = 0.7 ± 0.1, P < 0.01), whereas the percentage of two-variation fragments increased (baseline = 42.9 ± 3.6%, post-RIPC = 52.5 ± 3.0%, P < 0.01). These data indicate that repeated RIPC is necessary to elicit changes in sympathovagal balance, specifically resulting in increased vagal and decreased sympathetic activity.
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Frecuencia Cardíaca , Precondicionamiento Isquémico , Sistema Nervioso Parasimpático/fisiología , Adulto , Femenino , Corazón/fisiología , Hemodinámica , Humanos , Masculino , Nervio Vago/fisiología , Adulto JovenRESUMEN
The exercise pressor reflex (EPR) is engaged upon the activation of group III/IV skeletal muscle afferents and is one of the principal mediators of cardiovascular responses to exercise. This review explores the hypothesis that afferent signals from EPR communicate via GABAergic contacts within the brain stem to evoke parasympathetic withdrawal and sympathoexcitation to increase cardiac output, peripheral resistance, and blood pressure during exercise.
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Vías Aferentes/fisiología , Fenómenos Fisiológicos Cardiovasculares , Ejercicio Físico/fisiología , Neuronas GABAérgicas/fisiología , Músculo Esquelético/inervación , Núcleo Solitario/fisiología , Animales , Presión Sanguínea/fisiología , Gasto Cardíaco/fisiología , Humanos , Sistema Nervioso Simpático/fisiología , Resistencia Vascular/fisiologíaRESUMEN
Remote limb ischemic preconditioning (RIPC) has shown to improve dynamic postural control in humans. However, studies on the underlying adaptations of spinal cord networks have never been performed. The present work addresses this issue by investigating parameters from the soleus H-reflex recruitment curve (RC), presynaptic mechanisms of reflex modulation (presynaptic inhibition-PSI, and post activation depression-PAD), and the excursion of the center of pressure (CP) recorded during 1 min in upright stance over a compliant surface. A sham ischemic protocol (partial obstruction of blood flow) was applied to the contralateral thigh along four consecutive days. The same procedure was repeated with full obstruction (RIPC) three days after ending the sham protocol. Data were collected before and after both sham and RIPC protocols. The follow-up data were collected five days after the last ischemic intervention. Significant reduction was detected for both the fast oscillations of the CP (higher frequency components) and the parameter estimated from the RC corresponding to the high amplitude H-reflexes (p < 0.05). Even though the magnitude of effects was similar, it was washed out within three days after sham, but persisted for at least five days after RIPC. No significant differences were found for PSI and PAD levels across conditions. These findings indicate that RIPC leads to enduring changes in spinal cord excitability for the latest reflexively recruited motoneurons, along with improvement in balance control. However, these adaptations were not mediated by the presynaptic mechanisms currently assessed.
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Adaptación Fisiológica/fisiología , Fenómenos Electrofisiológicos/fisiología , Reflejo H/fisiología , Precondicionamiento Isquémico , Extremidad Inferior/fisiología , Músculo Esquelético/fisiología , Equilibrio Postural/fisiología , Médula Espinal/fisiología , Adulto , Electromiografía , Humanos , Masculino , Adulto JovenRESUMEN
KEY POINTS: The activation of the group III/IV skeletal muscle afferents is one of the principal mediators of cardiovascular responses to exercise; however, the neuronal circuitry mechanisms that are involved during the activation of group III/IV muscle afferents in humans remain unknown. Recently, we showed that GABAergic mechanisms are involved in the cardiac vagal withdrawal during the activation of mechanically sensitive (predominantly mediated by group III fibres) skeletal muscle afferents in humans. In the present study, we found that increases in muscle sympathetic nerve activity and mean blood pressure during isometric handgrip exercise and postexercise ischaemia were significantly greater after the oral administration of diazepam, a benzodiazepine that increases GABAA activity, but not after placebo administration in young healthy subjects. These findings indicate for the first time that GABAA receptors modulate sympathetic vasomotor outflow and the pressor responses to activation of metabolically sensitive (predominantly mediated by group IV fibres) skeletal muscle afferents in humans. ABSTRACT: Animal studies have indicated that GABAA receptors are involved in the neuronal circuitry of the group III/IV skeletal muscle afferent activation-induced neurocardiovascular responses to exercise. In the present study, we aimed to determine whether GABAA receptors modulate the neurocardiovascular responses to activation of metabolically sensitive (predominantly mediated by group IV fibres) skeletal muscle afferents in humans. In a randomized, double-blinded, placebo-controlled and cross-over design, 17 healthy subjects (eight women) performed 2 min of ischaemic isometric handgrip exercise at 30% of the maximal voluntary contraction followed by 2 min of postexercise ischaemia (PEI). Muscle sympathetic nerve activity (MSNA), blood pressure (BP) and heart rate (HR) were continuously measured and trials were conducted before and 60 min after the oral administration of either placebo or diazepam (10 mg), a benzodiazepine that enhances GABAA activity. At rest, MSNA was reduced, whereas HR and BP did not change after diazepam administration. During ischaemic isometric handgrip, greater MSNA (pre: ∆13 ± 9 bursts min-1 vs. post: ∆29 ± 15 bursts min-1 , P < 0.001), HR (pre: ∆23 ± 11 beats min-1 vs. post: ∆31 ± 17 beats min-1 , P < 0.01) and mean BP (pre: ∆33 ± 12 mmHg vs. post: ∆37 ± 12 mmHg, P < 0.01) responses were observed after diazepam. During PEI, MSNA and mean BP remained elevated from baseline before diazepam (∆10 ± 8 bursts min-1 and ∆25 ± 14 mmHg, respectively) and these elevations were increased after diazepam (∆17 ± 12 bursts min-1 and ∆28 ± 13 mmHg, respectively) (P ≤ 0.05). Importantly, placebo pill had no effect on neural, cardiac and pressor responses. These findings demonstrate for the first time that GABAA receptors modulate MSNA and the pressor responses to skeletal muscle metaboreflex activation in humans.