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1.
Am J Physiol Heart Circ Physiol ; 317(7): H1-H12, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31002284

RESUMO

The purpose of the present study was to test the hypothesis that doxorubicin (DX) and cyclophosphamide (CY) adjuvant chemotherapy (CHT) acutely impairs neurovascular and hemodynamic responses in women with breast cancer. Sixteen women (age: 47.0 ± 2.0 yr; body mass index: 24.2 ± 1.5 kg/m) with stage II-III breast cancer and indication for adjuvant CHT underwent two experimental sessions, saline (SL) and CHT. In the CHT session, DX (60 mg/m2) and CY (600 mg/m2) were administered over 45 min. In the SL session, a matching SL volume was infused in 45 min. Muscle sympathetic nerve activity (MSNA) from peroneal nerve (microneurography), calf blood flow (CBF; plethysmography) and calf vascular conductance (CVC), heart rate (HR; electrocardiography), and beat-to-beat blood pressure (BP; finger plethysmography) were measured at rest before, during, and after each session. Venous blood samples (5 ml) were collected before and after both sessions for assessment of circulating endothelial microparticles (EMPs; flow cytometry), a surrogate marker for endothelial damage. MSNA and BP responses were increased (P < 0.001), whereas CBF and CVC responses were decreased (P < 0.001), during and after CHT session when compared with SL session. Interestingly, the vascular alterations were also observed at the molecular level through an increased EMP response to CHT (P = 0.03, CHT vs. SL session). No difference in HR response was observed (P > 0.05). Adjuvant CHT with DX and CY in patients treated for breast cancer increases sympathetic nerve activity and circulating EMP levels and, in addition, reduces muscle vascular conductance and elevates systemic BP. These responses may be early signs of CHT-induced cardiovascular alterations and may represent potential targets for preventive interventions. NEW & NOTEWORTHY It is known that chemotherapy regimens increase the risk of cardiovascular events in patients treated for cancer. Here, we identified that a single cycle of adjuvant chemotherapy with doxorubicin and cyclophosphamide in women treated for breast cancer dramatically increases sympathetic nerve activity and circulating endothelial microparticle levels, reduces the muscle vascular conductance, and elevates systemic blood pressure.

2.
Motriz (Online) ; 25(1): e101902, 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1020084

RESUMO

Abstract Aim: This study tested the hypothesis that: 1- the exercise training would improve the heart rate recovery (HRR) decline after maximal exercise test in hypertensive patients and; 2- the exercise training would normalize HRR decline when compared to normotensive individuals. Methods: Sixteen hypertensive patients were consecutively allocated into two groups: Exercise-trained (n = 9, 47±2 years) and untrained (n = 7, 42±3 years). An exercise-trained normotensive group (n = 11, 41±2 years) was also studied. Heart rate was evaluated by electrocardiogram. The autonomic function was evaluated based on heart rate changes on the first and the second min of recovery after the maximal exercise test. Exercise training consisted of three 60-minute exercise sessions/week for 4 months. Results: In hypertensive patients, exercise training significantly increased the HRR decline in the first (-19±2 vs. -34±3 bpm, P = 0.001) and second (-33±3 vs. -49±2 bpm, P = 0.006) minutes after the maximal exercise test. In addition, after exercise training, the initial differences in the HRR decline after exercise between hypertensive patients and normotensive individuals were no longer observed (first minute: -34±3 vs. -29±3 bpm, P = 0.52, and second minute: -49±2 vs. -47±4 bpm, P = 0.99). Conclusion: Hypertension causes a delay in HRR after the maximal exercise test yet the exercise training normalizes HRR during the post-exercise period in hypertensive patients.

3.
Sleep Breath ; 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29948856

RESUMO

PURPOSE: We tested the hypothesis that (i) diet associated with exercise would improve arterial baroreflex (ABR) control in metabolic syndrome (MetS) patients with and without obstructive sleep apnea (OSA) and (ii) the effects of this intervention would be more pronounced in patients with OSA. METHODS: Forty-six MetS patients without (noOSA) and with OSA (apnea-hypopnea index, AHI > 15 events/h) were allocated to no treatment (control, C) or hypocaloric diet (- 500 kcal/day) associated with exercise (40 min, bicycle exercise, 3 times/week) for 4 months (treatment, T), resulting in four groups: noOSA-C (n = 10), OSA-C (n = 12), noOSA-T (n = 13), and OSA-T (n = 11). Muscle sympathetic nerve activity (MSNA), beat-to-beat BP, and spontaneous arterial baroreflex function of MSNA (ABRMSNA, gain and time delay) were assessed at study entry and end. RESULTS: No significant changes occurred in C groups. In contrast, treatment in both patients with and without OSA led to a significant decrease in weight (P < 0.05) and the number of MetS factors (P = 0.03). AHI declined only in the OSA-T group (31 ± 5 to 17 ± 4 events/h, P < 0.05). Systolic BP decreased in both treatment groups, and diastolic BP decreased significantly only in the noOSA-T group. Treatment decreased MSNA in both groups. Compared with baseline, ABRMSNA gain increased in both OSA-T (13 ± 1 vs. 24 ± 2 a.u./mmHg, P = 0.01) and noOSA-T (27 ± 3 vs. 37 ± 3 a.u./mmHg, P = 0.03) groups. The time delay of ABRMSNA was reduced only in the OSA-T group (4.1 ± 0.2 s vs. 2.8 ± 0.3 s, P = 0.04). CONCLUSIONS: Diet associated with exercise improves baroreflex control of sympathetic nerve activity and MetS components in patients with MetS regardless of OSA.

4.
J Clin Hypertens (Greenwich) ; 19(9): 840-847, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28868764

RESUMO

Metabolic syndrome (MetS) causes autonomic alteration and vascular dysfunction. The authors investigated whether impaired fasting glucose (IFG) is the main cause of vascular dysfunction via elevated sympathetic tone in nondiabetic patients with MetS. Pulse wave velocity, muscle sympathetic nerve activity (MSNA), and forearm vascular resistance was measured in patients with MetS divided according to fasting glucose levels: (1) MetS+IFG (blood glucose ≥100 mg/dL) and (2) MetS-IFG (<100 mg/dL) compared with healthy controls. Patients with MetS+IFG had higher pulse wave velocity than patients with MetS-IFG and controls (median 8.0 [interquartile range, 7.2-8.6], 7.3 [interquartile range, 6.9-7.9], and 6.9 [interquartile range, 6.6-7.2] m/s, P=.001). Patients with MetS+IFG had higher MSNA than patients with MetS-IFG and controls, and patients with MetS-IFG had higher MSNA than controls (31±1, 26±1, and 19±1 bursts per minute; P<.001). Patients with MetS+IFG were similar to patients with MetS-IFG but had higher forearm vascular resistance than controls (P=.008). IFG was the only predictor variable of MSNA. MSNA was associated with pulse wave velocity (R=.39, P=.002) and forearm vascular resistance (R=.30, P=.034). In patients with MetS, increased plasma glucose levels leads to an adrenergic burden that can explain vascular dysfunction.


Assuntos
Glicemia/análise , Intolerância à Glucose/complicações , Síndrome Metabólica/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Glicemia/metabolismo , Feminino , Intolerância à Glucose/epidemiologia , Intolerância à Glucose/fisiopatologia , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Estado Pré-Diabético/complicações , Estudos Prospectivos , Análise de Onda de Pulso/métodos , Fatores de Risco , Resistência Vascular/fisiologia , Rigidez Vascular/fisiologia , Circunferência da Cintura
5.
Front Neurosci ; 11: 162, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28424575

RESUMO

Heart failure (HF) is a complex syndrome representing the clinical endpoint of many cardiovascular diseases of different etiology. Given its prevalence, incidence and social impact, a better understanding of HF pathophysiology is paramount to implement more effective anti-HF therapies. Based on left ventricle (LV) performance, HF is currently classified as follows: (1) with reduced ejection fraction (HFrEF); (2) with mid-range EF (HFmrEF); and (3) with preserved EF (HFpEF). A central tenet of HFrEF pathophysiology is adrenergic hyperactivity, featuring increased sympathetic nerve discharge and a progressive loss of rhythmical sympathetic oscillations. The role of reflex mechanisms in sustaining adrenergic abnormalities during HFrEF is increasingly well appreciated and delineated. However, the same cannot be said for patients affected by HFpEF or HFmrEF, whom also present with autonomic dysfunction. Neural mechanisms of cardiovascular regulation act as "controller units," detecting and adjusting for changes in arterial blood pressure, blood volume, and arterial concentrations of oxygen, carbon dioxide and pH, as well as for humoral factors eventually released after myocardial (or other tissue) ischemia. They do so on a beat-to-beat basis. The central dynamic integration of all these afferent signals ensures homeostasis, at rest and during states of physiological or pathophysiological stress. Thus, the net result of information gathered by each controller unit is transmitted by the autonomic branch using two different codes: intensity and rhythm of sympathetic discharges. The main scope of the present article is to (i) review the key neural mechanisms involved in cardiovascular regulation; (ii) discuss how their dysfunction accounts for the hyperadrenergic state present in certain forms of HF; and (iii) summarize how sympathetic efferent traffic reveal central integration among autonomic mechanisms under physiological and pathological conditions, with a special emphasis on pathophysiological characteristics of HF.

6.
PLoS One ; 12(2): e0173061, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28235084

RESUMO

BACKGROUND: Gln27Glu (rs1042714) polymorphism of the ß2-adrenergic receptor (ADRB2) has been association with cardiovascular functionality in healthy subjects. However, it is unknown whether the presence of the ADRB2 Gln27Glu polymorphism influences neurovascular responses during exercise in patients with acute coronary syndromes (ACS). We tested the hypothesis that patients with ACS homozygous for the Gln allele would have increased muscle sympathetic nerve activity (MSNA) responses and decreased forearm vascular conductance (FVC) responses during exercise compared with patients carrying the Glu allele (Gln27Glu and Glu27Glu). In addition, exercise training would restore these responses in Gln27Gln patients. METHODS AND RESULTS: Thirty-days after an ischemic event, 61 patients with ACS without ventricular dysfunction were divided into 2 groups: (1) Gln27Gln (n = 35, 53±1years) and (2) Gln27Glu+Glu27Glu (n = 26, 52±2years). MSNA was directly measured using the microneurography technique, blood pressure (BP) was measured with an automatic oscillometric device, and blood flow was measured using venous occlusion plethysmography. MSNA, mean BP, and FVC were evaluated at rest and during a 3-min handgrip exercise. The MSNA (P = 0.02) and mean BP (P = 0.04) responses during exercise were higher in the Gln27Gln patients compared with that in the Gln27Glu+Glu27Glu patients. No differences were found in FVC. Two months of exercise training significantly decreased the MSNA levels at baseline (P = 0.001) and in their response during exercise (P = 0.02) in Gln27Gln patients, but caused no changes in Gln27Glu+Glu27Glu patients. Exercise training increased FVC responses in Gln27Glu+Glu27Glu patients (P = 0.03), but not in Gln27Gln patients. CONCLUSION: The exaggerated MSNA and mean BP responses during exercise suggest an increased cardiovascular risk in patients with ACS and Gln27Gln polymorphism. Exercise training emerges as an important strategy for restoring this reflex control. Gln27Glu polymorphism of ADRB2 influences exercise-induced vascular adaptation in patients with ACS.


Assuntos
Síndrome Coronariana Aguda/genética , Antebraço/irrigação sanguínea , Receptores Adrenérgicos beta 2/genética , Sistema Vasomotor , Síndrome Coronariana Aguda/fisiopatologia , Síndrome Coronariana Aguda/terapia , Terapia por Exercício , Feminino , Frequência do Gene , Estudos de Associação Genética , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular , Polimorfismo de Nucleotídeo Único , Fatores de Risco
7.
Am J Physiol Heart Circ Physiol ; 311(5): H1180-H1188, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27591218

RESUMO

Heart failure (HF) is characterized by decreased exercise capacity, attributable to neurocirculatory and skeletal muscle factors. Cardiac resynchronization therapy (CRT) and exercise training have each been shown to decrease muscle sympathetic nerve activity (MSNA) and increase exercise capacity in patients with HF. We hypothesized that exercise training in the setting of CRT would further reduce MSNA and vasoconstriction and would increase Ca2+-handling gene expression in skeletal muscle in patients with chronic systolic HF. Thirty patients with HF, ejection fraction <35% and CRT for 1 mo, were randomized into two groups: exercise-trained (ET, n = 14) and untrained (NoET, n = 16) groups. The following parameters were compared at baseline and after 4 mo in each group: V̇o2 peak, MSNA (microneurography), forearm blood flow, and Ca2+-handling gene expression in vastus lateralis muscle. After 4 mo, exercise duration and V̇o2 peak were significantly increased in the ET group (P = 0.04 and P = 0.01, respectively), but not in the NoET group. MSNA was significantly reduced in the ET (P = 0.001), but not in NoET, group. Similarly, forearm vascular conductance significantly increased in the ET (P = 0.0004), but not in the NoET, group. The expression of the Na+/Ca2+ exchanger (P = 0.01) was increased, and ryanodine receptor expression was preserved in ET compared with NoET. In conclusion, the exercise training in the setting of CRT improves exercise tolerance and neurovascular control and alters Ca2+-handling gene expression in the skeletal muscle of patients with systolic HF. These findings highlight the importance of including exercise training in the treatment of patients with HF even following CRT.


Assuntos
Cálcio/metabolismo , Terapia de Ressincronização Cardíaca , Terapia por Exercício , Exercício , Insuficiência Cardíaca/terapia , Acoplamento Neurovascular , Músculo Quadríceps/metabolismo , Sistema Nervoso Simpático/metabolismo , Ecocardiografia , Teste de Esforço , Tolerância ao Exercício , Feminino , Antebraço/irrigação sanguínea , Expressão Gênica , Insuficiência Cardíaca/genética , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/inervação , Músculo Esquelético/metabolismo , Consumo de Oxigênio , Músculo Quadríceps/inervação , RNA Mensageiro/metabolismo , Fluxo Sanguíneo Regional , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Trocador de Sódio e Cálcio/genética
8.
Obesity (Silver Spring) ; 23(8): 1582-90, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26148219

RESUMO

OBJECTIVE: Chemoreflex hypersensitity was caused by obstructive sleep apnea (OSA) in patients with metabolic syndrome (MetS). This study tested the hypothesis that hypocaloric diet and exercise training (D+ET) would improve peripheral and central chemoreflex sensitivity in patients with MetS and OSA. METHODS: Patients were assigned to: (1) D+ET (n = 16) and (2) no intervention control (C, n = 8). Minute ventilation (VE, pre-calibrated pneumotachograph) and muscle sympathetic nerve activity (MSNA, microneurography) were evaluated during peripheral chemoreflex sensitivity by inhalation of 10% O2 and 90% N2 with CO2 titrated and central chemoreflex by 7% CO2 and 93% O2 for 3 min at study entry and after 4 months. RESULTS: Peak VO2 was increased by D+ET; body weight, waist circumference, glucose levels, systolic/diastolic blood pressure, and apnea-hypopnea index (AHI) (34 ± 5.1 vs. 18 ± 3.2 events/h, P = 0.04) were reduced by D+ET. MSNA was reduced by D+ET at rest and in response to hypoxia (8.6 ± 1.2 vs. 5.4 ± 0.6 bursts/min, P = 0.02), and VE in response to hypercapnia (14.8 ± 3.9 vs. 9.1 ± 1.2 l/min, P = 0.02). No changes were found in the C group. A positive correlation was found between AHI and MSNA absolute changes (R = 0.51, P = 0.01) and body weight and AHI absolute changes (R = 0.69, P < 0.001). CONCLUSIONS: Sympathetic peripheral and ventilatory central chemoreflex sensitivity was improved by D+ET in MetS+OSA patients, which may be associated with improvement in sleep pattern.


Assuntos
Dieta Redutora , Exercício , Síndrome Metabólica/complicações , Obesidade/terapia , Apneia Obstrutiva do Sono/complicações , Sistema Nervoso Simpático/fisiopatologia , Adulto , Dióxido de Carbono/metabolismo , Células Quimiorreceptoras/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Sistema Nervoso Simpático/metabolismo , Resultado do Tratamento
9.
Am J Physiol Heart Circ Physiol ; 308(9): H1096-102, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25747752

RESUMO

Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). The purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF ≤ 40%, peak V̇o2 ≤ 20 ml·kg(-1)·min(-1) were divided into two groups: untrained (UT, n = 13, 57 ± 3 years) and exercise trained (ET, n = 13, 49 ± 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. The gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. The gain and time delay of ABRMSNA were unchanged in the ET patients. In contrast, the gain of ABRMSNA was significantly reduced [3.5 ± 0.7 vs. 1.8 ± 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 ± 0.8 vs. 7.9 ± 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients.


Assuntos
Pressão Arterial , Barorreflexo , Sistema Cardiovascular/inervação , Terapia por Exercício , Insuficiência Cardíaca/terapia , Músculo Esquelético/inervação , Sistema Nervoso Simpático/fisiopatologia , Adulto , Idoso , Ciclismo , Brasil , Doença Crônica , Terapia por Exercício/métodos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
10.
Sleep ; 38(7): 1059-66, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25669187

RESUMO

STUDY OBJECTIVES: The attenuation of heart rate recovery after maximal exercise (ΔHRR) is independently impaired by obstructive sleep apnea (OSA) and metabolic syndrome (MetS). Therefore, we tested the hypotheses: (1) MetS + OSA restrains ΔHRR; and (2) Sympathetic hyperactivation is involved in this impairment. DESIGN: Cross-sectional study. PARTICIPANTS: We studied 60 outpatients in whom MetS had been newly diagnosed (ATP III), divided according to apnea-hypopnea index (AHI) ≥ 15 events/h in MetS + OSA (n = 30, 49 ± 1.7 y) and AHI < 15 events/h in MetS - OSA (n = 30, 46 ± 1.4 y). Normal age-matched healthy control subjects (C) without MetS and OSA were also enrolled (n = 16, 46 ± 1.7 y). INTERVENTIONS: Polysomnography, microneurography, cardiopulmonary exercise test. MEASUREMENTS AND RESULTS: We evaluated OSA (AHI - polysomnography), muscle sympathetic nerve activity (MSNA - microneurography) and cardiac autonomic activity (LF = low frequency, HF = high frequency, LF/HF = sympathovagal balance) based on spectral analysis of heart rate (HR) variability. ΔHRR was calculated (peak HR minus HR at first, second, and fourth minute of recovery) after cardiopulmonary exercise test. MetS + OSA had higher MSNA and LF, and lower HF than MetS - OSA and C. Similar impairment occurred in MetS - OSA versus C (interaction, P < 0.01). MetS + OSA had attenuated ΔHRR at first, second, and at fourth minute than did C, and attenuated ΔHRR at fourth minute than did MetS - OSA (interaction, P < 0.001). Compared with C, MetS - OSA had attenuated ΔHRR at second and fourth min (interaction, P < 0.001). Further analysis showed association of the ΔHRR (first, second, and fourth minute) and AHI, MSNA, LF and HF components (P < 0.05 for all associations). CONCLUSIONS: The attenuation of heart rate recovery after maximal exercise is impaired to a greater degree where metabolic syndrome (MetS) is associated with moderate to severe obstructive sleep apnea (OSA) than by MetS with no or mild or no OSA. This is at least partly explained by sympathetic hyperactivity.


Assuntos
Exercício/fisiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/fisiopatologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Nervo Vago/fisiologia , Adulto , Estudos Transversais , Teste de Esforço , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia
11.
Am J Physiol Heart Circ Physiol ; 307(11): H1655-66, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25305179

RESUMO

Previous studies have demonstrated that muscle mechanoreflex and metaboreflex controls are altered in heart failure (HF), which seems to be due to changes in cyclooxygenase (COX) pathway and changes in receptors on afferent neurons, including transient receptor potential vanilloid type-1 (TRPV1) and cannabinoid receptor type-1 (CB1). The purpose of the present study was to test the hypotheses: 1) exercise training (ET) alters the muscle metaboreflex and mechanoreflex control of muscle sympathetic nerve activity (MSNA) in HF patients. 2) The alteration in metaboreflex control is accompanied by increased expression of TRPV1 and CB1 receptors in skeletal muscle. 3) The alteration in mechanoreflex control is accompanied by COX-2 pathway in skeletal muscle. Thirty-four consecutive HF patients with ejection fractions <40% were randomized to untrained (n = 17; 54 ± 2 yr) or exercise-trained (n = 17; 56 ± 2 yr) groups. MSNA was recorded by microneurography. Mechanoreceptors were activated by passive exercise and metaboreceptors by postexercise circulatory arrest (PECA). COX-2 pathway, TRPV1, and CB1 receptors were measured in muscle biopsies. Following ET, resting MSNA was decreased compared with untrained group. During PECA (metaboreflex), MSNA responses were increased, which was accompanied by the expression of TRPV1 and CB1 receptors. During passive exercise (mechanoreflex), MSNA responses were decreased, which was accompanied by decreased expression of COX-2, prostaglandin-E2 receptor-4, and thromboxane-A2 receptor and by decreased in muscle inflammation, as indicated by increased miRNA-146 levels and the stable NF-κB/IκB-α ratio. In conclusion, ET alters muscle metaboreflex and mechanoreflex control of MSNA in HF patients. This alteration with ET is accompanied by alteration in TRPV1 and CB1 expression and COX-2 pathway and inflammation in skeletal muscle.


Assuntos
Terapia por Exercício , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/terapia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Reflexo/fisiologia , Adulto , Idoso , Doença Crônica , Ciclo-Oxigenase 2/fisiologia , Teste de Esforço , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Receptor CB1 de Canabinoide/biossíntese , Transdução de Sinais/fisiologia , Volume Sistólico/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Canais de Cátion TRPV/biossíntese
12.
Am J Physiol Heart Circ Physiol ; 304(7): H1038-44, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23355343

RESUMO

The incidence and strength of muscle sympathetic nerve activity (MSNA) depend on the magnitude (gain) and latency (time delay) of the arterial baroreflex control (ABR). However, the impact of metabolic syndrome (MetS) and obstructive sleep apnea (OSA) on oscillatory pattern of MSNA and time delay of the ABR of sympathetic activity is unknown. We tested the hypothesis that MetS and OSA would impair the oscillatory pattern of MSNA and the time delay of the ABR of sympathetic activity. Forty-three patients with MetS were allocated into two groups according to the presence of OSA (MetS + OSA, n = 21; and MetS - OSA, n = 22). Twelve aged-paired healthy controls (C) were also studied. OSA (apnea-hypopnea index > 15 events/h) was diagnosed by polysomnography. We recorded MSNA (microneurography), blood pressure (beat-to-beat basis), and heart rate (EKG). Oscillatory pattern of MSNA was evaluated by autoregressive spectral analysis and the ABR of MSNA (ABRMSNA, sensitivity and time delay) by bivariate autoregressive analysis. Patients with MetS + OSA had decreased oscillatory pattern of MSNA compared with MetS - OSA (P < 0.01) and C (P < 0.001). The sensitivity of the ABRMSNA was lower and the time delay was greater in MetS + OSA compared with MetS - OSA (P < 0.001 and P < 0.01, respectively) and C (P < 0.001 and P < 0.001, respectively). Patients with MetS - OSA showed decreased oscillatory pattern of MSNA compared with C (P < 0.01). The sensitivity of the ABRMSNA was lower in MetS - OSA than in C group (P < 0.001). In conclusion, MetS decreases the oscillatory pattern of MSNA and the magnitude of the ABRMSNA. OSA exacerbates these autonomic dysfunctions and further increases the time delay of the baroreflex response of MSNA.


Assuntos
Barorreflexo/fisiologia , Síndrome Metabólica/fisiopatologia , Tempo de Reação , Apneia Obstrutiva do Sono/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adulto , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico
13.
Sleep ; 36(1): 41-9, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23288970

RESUMO

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is often observed in patients with metabolic syndrome (MetS). In addition, the association of MetS and OSA substantially increases sympathetic nerve activity. However, the mechanisms involved in sympathetic hyperactivation in patients with MetS + OSA remain to be clarified. We tested the hypothesis that chemoreflex sensitivity is heightened in patients with MetS and OSA. DESIGN: Prospective clinical study. PARTICIPANTS: Forty-six patients in whom MetS was newly diagnosed (ATP-III) were allocated into: (1) MetS + OSA (n = 24, 48 ± 1.8 yr); and (2) MetS - OSA (n = 22, 44 ± 1.7 yr). Eleven normal control subjects were also studied (C, 47 ± 2.3 yr). MEASUREMENTS: OSA was defined as an apnea-hypopnea index ≥ 15 events/hr (polysomnography). Muscle sympathetic nerve activity (MSNA) was measured by microneurography technique. Peripheral chemoreflex sensitivity was assessed by inhalation of 10% oxygen and 90% nitrogen (carbon dioxide titrated), and central chemoreflex sensitivity by 7% carbon dioxide and 93% oxygen. RESULTS: Physical characteristics and MetS measures were similar between MetS + OSA and MetS - OSA. MSNA was higher in MetS + OSA patients compared with MetS - OSA and C (33 ± 1.3 versus 28 ± 1.2 and 18 ± 2.2 bursts/min, P < 0.05). Isocapnic hypoxia caused a greater increase in MSNA in MetS + OSA than MetS - OSA and C (P = 0.03). MSNA in response to hyperoxic hypercapnia was greater in MetS + OSA compared with C (P = 0.005). Further analysis showed a significant association between baseline MSNA and peripheral (P < 0.01) and central (P < 0.01) chemoreflex sensitivity. Min ventilation in response to hyperoxic hypercapnia was greater in MetS + OSA compared with C (P = 0.001). CONCLUSION: OSA increases sympathetic peripheral and central chemoreflex response in patients with MetS, which seems to explain, at least in part, the increase in sympathetic nerve activity in these patients. In addition, OSA increases ventilatory central chemoreflex response in patients with MetS.


Assuntos
Células Quimiorreceptoras/metabolismo , Síndrome Metabólica/complicações , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adulto , Análise de Variância , Dióxido de Carbono/metabolismo , Feminino , Humanos , Hipercapnia/complicações , Hipercapnia/metabolismo , Hipercapnia/fisiopatologia , Hipóxia/complicações , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Nitrogênio/metabolismo , Oxigênio/metabolismo , Polissonografia/métodos , Estudos Prospectivos , Ventilação Pulmonar , Reflexo , Apneia Obstrutiva do Sono/metabolismo , Sistema Nervoso Simpático/metabolismo
15.
Eur J Appl Physiol ; 113(3): 671-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22918560

RESUMO

Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.


Assuntos
Ansiedade/complicações , Sistema Nervoso Autônomo/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Síndrome Metabólica/complicações , Síndrome Metabólica/fisiopatologia , Transtornos do Humor/complicações , Adulto , Ansiedade/epidemiologia , Ansiedade/fisiopatologia , Doenças do Sistema Nervoso Autônomo/epidemiologia , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/inervação , Estudos de Casos e Controles , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Transtornos do Humor/fisiopatologia , Fatores de Risco , Sistema Nervoso Simpático/fisiopatologia
16.
Hypertension ; 60(3): 669-76, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22802226

RESUMO

We described recently that systemic hypoxia provokes vasoconstriction in heart failure (HF) patients. We hypothesized that either the exaggerated muscle sympathetic nerve activity and/or endothelial dysfunction mediate the blunted vasodilatation during hypoxia in HF patients. Twenty-seven HF patients and 23 age-matched controls were studied. Muscle sympathetic nerve activity was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O(2) and 90% N(2)). Basal muscle sympathetic nerve activity was greater and basal FBF was lower in HF patients versus controls. During hypoxia, muscle sympathetic nerve activity responses were greater in HF patients, and forearm vasodilatation in HF was blunted versus controls. Phentolamine increased FBF responses in both groups, but the increase was lower in HF patients. Phentolamine and N(G)-monomethyl-l-arginine infusion did not change FBF responses in HF but markedly blunted the vasodilatation in controls. FBF responses to hypoxia in the presence of vitamin C were unchanged and remained lower in HF patients versus controls. In conclusion, muscle vasoconstriction in response to hypoxia in HF patients is attributed to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies.


Assuntos
Células Quimiorreceptoras/fisiologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Músculo Liso Vascular/inervação , Músculo Liso Vascular/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Vasodilatação/fisiologia , Adulto , Ácido Ascórbico/farmacologia , Estudos de Casos e Controles , Antebraço/irrigação sanguínea , Hemodinâmica/fisiologia , Humanos , Hipóxia/fisiopatologia , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Fentolamina/farmacologia , Sistema Nervoso Simpático/fisiopatologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasodilatação/efeitos dos fármacos , ômega-N-Metilarginina/farmacologia
17.
Sleep ; 33(9): 1193-9, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20857866

RESUMO

STUDY OBJECTIVES: Metabolic syndrome (MetSyn) increases overall cardiovascular risk. MetSyn is also strongly associated with obstructive sleep apnea (OSA), and these 2 conditions share similar comorbidities. Whether OSA increases cardiovascular risk in patients with the MetSyn has not been investigated. We examined how the presence of OSA in patients with MetSyn affected hemodynamic and autonomic variables associated with poor cardiovascular outcome. DESIGN: Prospective clinical study. PARTICIPANTS: We studied 36 patients with MetSyn (ATP-III) divided into 2 groups matched for age and sex: (1) MetSyn+OSA (n = 18) and (2) MetSyn-OSA (n = 18). MEASUREMENTS: OSA was defined by an apnea-hypopnea index (AHI) > 15 events/hour by polysomnography. We recorded muscle sympathetic nerve activity (MSNA - microneurography), heart rate (HR), and blood pressure (BP - Finapres). Baroreflex sensitivity (BRS) was analyzed by spontaneous BP and HR fluctuations. RESULTS: MSNA (34 +/- 2 vs 28 +/- 1 bursts/min, P = 0.02) and mean BP (111 +/- 3 vs. 99 +/- 2 mm Hg, P = 0.003) were higher in patients with MetSyn+OSA versus patients with MetSyn-OSA. Patients with MetSyn+OSA had lower spontaneous BRS for increases (7.6 +/- 0.6 vs 12.2 +/- 1.2 msec/mm Hg, P = 0.003) and decreases (7.2 +/- 0.6 vs 11.9 +/- 1.6 msec/mm Hg, P = 0.01) in BP. MSNAwas correlated with AHI (r = 0.48; P = 0.009) and minimum nocturnal oxygen saturation (r = -0.38, P = 0.04). CONCLUSION: Patients with MetSyn and comorbid OSA have higher BP, higher sympathetic drive, and diminished BRS, compared with patients with MetSyn without OSA. These adverse cardiovascular and autonomic consequences of OSA may be associated with poorer outcomes in these patients. Moreover, increased BP and sympathetic drive in patients with MetSyn+OSA may be linked, in part, to impairment of baroreflex gain.


Assuntos
Doenças Cardiovasculares/etiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/fisiopatologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Barorreflexo , Pressão Sanguínea , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Frequência Cardíaca , Humanos , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Consumo de Oxigênio , Fatores de Risco , Apneia Obstrutiva do Sono/metabolismo , Vasodilatação
18.
Physiol Genomics ; 42A(1): 71-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20605946

RESUMO

Allele T at promoter region of the eNOS gene has been associated with an increase in coronary disease mortality, suggesting that this allele increases susceptibility for endothelial dysfunction. In contrast, exercise training improves endothelial function. Thus, we hypothesized that: 1) Muscle vasodilatation during exercise is attenuated in individuals homozygous for allele T, and 2) Exercise training improves muscle vasodilatation in response to exercise for TT genotype individuals. From 133 preselected healthy individuals genotyped for the T786C polymorphism, 72 participated in the study: TT (n = 37; age 27 ± 1 yr) and CT+CC (n = 35; age 26 ± 1 yr). Forearm blood flow (venous occlusion plethysmography) and blood pressure (oscillometric automatic cuff) were evaluated at rest and during 30% handgrip exercise. Exercise training consisted of three sessions per week for 18 wk, with intensity between anaerobic threshold and respiratory compensation point. Resting forearm vascular conductance (FVC, P = 0.17) and mean blood pressure (P = 0.70) were similar between groups. However, FVC responses during handgrip exercise were significantly lower in TT individuals compared with CT+CC individuals (0.39 ± 0.12 vs. 1.08 ± 0.27 units, P = 0.01). Exercise training significantly increased peak VO(2) in both groups, but resting FVC remained unchanged. This intervention significantly increased FVC response to handgrip exercise in TT individuals (P = 0.03), but not in CT+CC individuals (P = 0.49), leading to an equivalent FVC response between TT and CT+CC individuals (1.05 ± 0.18 vs. 1.59 ± 0.27 units, P = 0.27). In conclusion, exercise training improves muscle vasodilatation in response to exercise in TT genotype individuals, demonstrating that genetic variants influence the effects of interventions such as exercise training.


Assuntos
Exercício/fisiologia , Músculo Esquelético/irrigação sanguínea , Óxido Nítrico Sintase Tipo III/genética , Vasodilatação/fisiologia , Adolescente , Adulto , Feminino , Genótipo , Frequência Cardíaca/genética , Frequência Cardíaca/fisiologia , Humanos , Masculino , Vasodilatação/genética , Adulto Jovem
19.
Lipids Health Dis ; 9: 55, 2010 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-20515505

RESUMO

BACKGROUND: Forearm blood flow responses during mental stress are greater in individuals homozygous for the Glu27 allele. A high-fat meal is associated with impaired endothelium-dependent dilatation. We investigated the impact of high-fat ingestion on the muscle vasodilatory responses during mental stress in individuals with the Glu27 allele and those with the Gln27 allele of the beta2-adrenoceptor gene. METHODS: A total of 162 preselected individuals were genotyped for the Glu27Gln beta2-adrenoceptor polymorphism. Twenty-four individuals participated in the study. Fourteen were homozygous for the Gln27 allele (Gln27Gln, 40 +/- 2 years; 64 +/- 2 kg), and 10 were homozygous for the Glu27 allele (Glu27Glu, 40 +/- 3 years; 65 +/- 3 kg). Forearm blood flow was evaluated by venous occlusion plethysmography before and after ingestion of 62 g of fat. RESULTS: The high-fat meal caused no changes in baseline forearm vascular conductance (FVC, 2.2 +/- 0.1 vs. 2.4 +/- 0.2; P = 0.27, respectively), but reduced FVC responses to mental stress (1.5 +/- 0.2 vs. 0.8 +/- 0.2 units; P = 0.04). When volunteers were divided according to their genotypes, baseline FVC was not different between groups (Glu27Glu = 2.4 +/- 0.1 vs. Gln27Gln = 2.1 +/- 0.1 units; P = 0.08), but it was significantly greater in Glu27Glu individuals during mental stress (1.9 +/- 0.4 vs. 1.0 +/- 0.3 units; P = 0.04). High-fat intake eliminated the difference in FVC responses between Glu27Glu and Gln27Gln individuals (FVC, 1.3 +/- 0.4 vs. 1.2 +/- 0.4; P = 0.66, respectively). CONCLUSION: These findings demonstrate that a high-fat meal impairs muscle vasodilatation responses to mental stress in humans. However, this reduction can be attributed to the presence of the homozygous Glu27 allele of the beta2-adrenoceptor gene.


Assuntos
Gorduras na Dieta/farmacologia , Músculo Esquelético/irrigação sanguínea , Polimorfismo Genético , Receptores Adrenérgicos beta 2/genética , Estresse Psicológico/fisiopatologia , Vasodilatação/fisiologia , Adulto , Gorduras na Dieta/administração & dosagem , Genótipo , Humanos , Fluxo Sanguíneo Regional , Vasodilatação/efeitos dos fármacos
20.
Physiol Genomics ; 37(2): 99-107, 2009 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-19158254

RESUMO

The influence of Glu298Asp endothelial nitric oxide synthase (eNOS) polymorphism in exercise-induced reflex muscle vasodilatation is unknown. We hypothesized that nonexercising forearm blood flow (FBF) responses during handgrip isometric exercise would be attenuated in individuals carrying the Asp298 allele. In addition, these responses would be mediated by reduced eNOS function and NO-mediated vasodilatation or sympathetic vasoconstriction. From 287 volunteers previously genotyped, we selected 33 healthy individuals to represent three genotypes: Glu/Glu [n = 15, age 43 +/- 3 yr, body mass index (BMI) 22.9 +/- 0.3 kg/m(2)], Glu/Asp (n = 9, age 41 +/- 3 yr, BMI 23.7 +/- 1.0 kg/m(2)), and Asp/Asp (n = 9, age 40 +/- 4 yr, BMI 23.5 +/- 0.9 kg/m(2)). Heart rate (HR), mean blood pressure (MBP), and FBF (plethysmography) were recorded for 3 min at baseline and 3 min during isometric handgrip exercise. Baseline HR, MBP, FBF, and forearm vascular conductance (FVC) were similar among genotypes. FVC responses to exercise were significantly lower in Asp/Asp when compared with Glu/Asp and Glu/Glu (Delta = 0.07 +/- 0.14 vs. 0.64 +/- 0.20 and 0.57 +/- 0.09 units, respectively; P = 0.002). Further studies showed that intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA) did not change FVC responses to exercise in Asp/Asp, but significantly reduced FVC in Glu/Glu (Delta = 0.79 +/- 0.14 vs. 0.14 +/- 0.09 units). Thus the differences between Glu/Glu and Asp/Asp were no longer observed (P = 0.62). l-NMMA + phentolamine increased similarly FVC responses to exercise in Glu/Glu and Asp/Asp (P = 0.43). MBP and muscle sympathetic nerve activity increased significant and similarly throughout experimental protocols in Glu/Glu and Asp/Asp. Individuals who are homozygous for the Asp298 allele of the eNOS enzyme have attenuated nonexercising muscle vasodilatation in response to exercise. This genotype difference is due to reduced eNOS function and NO-mediated vasodilatation, but not sympathetic vasoconstriction.


Assuntos
Exercício/fisiologia , Contração Isométrica/fisiologia , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético , Adulto , Substituição de Aminoácidos , Análise de Variância , Pressão Sanguínea , Índice de Massa Corporal , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Feminino , Antebraço/irrigação sanguínea , Frequência do Gene , Genótipo , Força da Mão/fisiologia , Frequência Cardíaca , Humanos , Infusões Intra-Arteriais , Contração Isométrica/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Vasodilatação/efeitos dos fármacos , ômega-N-Metilarginina/administração & dosagem , ômega-N-Metilarginina/farmacologia
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