RESUMO
Microneurographic recordings of muscle sympathetic nerve activity (MSNA) and the succeeding changes in beat-to-beat blood pressure (i.e., sympathetic transduction) provide important insights into the neural control of the circulation in humans. Despite its widespread use, the reliability of this technique remains unknown. Herein, we assessed the intra- and interday test-retest reliability of signal-averaging sympathetic transduction to blood pressure. Data were analyzed from 15 (9 M/6 F) young, healthy participants who completed two baseline recordings of fibular nerve MSNA separated by 60 min (intraday). The interday reliability was obtained in a subset of participants (n = 13, 9 M/4 F) who completed a follow-up MSNA study. Signal-averaging sympathetic transduction was quantified as peak change in diastolic (DBP) and mean arterial pressure (MAP) following a burst of MSNA. Analyses were also computed considering different MSNA burst sizes (quartiles of normalized MSNA) and burst patterns (singlets, couplets, triplets, and quadruplets+), as well as nonburst responses. Intraclass-correlation coefficients (ICCs) were used as the main reliability measure. Peak changes in MAP [intraday: ICC = 0.76 (0.30-0.92), P = 0.006; interday: ICC = 0.91 (0.63-0.97), P < 0.001] demonstrated very good to excellent reliability. Sympathetic transduction of MSNA burst size displayed moderate to very good reliability, though the reliability of MSNA burst pattern was poor to very good. Nonburst responses revealed poor intraday [ICC = 0.37 (-1.05 to 0.80), P = 0.21], but very good interday [ICC = 0.76 (0.18-0.93), P = 0.01] reliability. Intraday reliability measures were consistently lower than interday reliability. Similar results were obtained using DBP. Collectively, these findings provide evidence that the burst-triggering signal-averaging technique is a reliable measure of sympathetic transduction to blood pressure in young, healthy adults.NEW & NOTEWORTHY We found that signal-averaging sympathetic transduction to blood pressure displayed very good to excellent intra- and interday test-retest reliability in healthy, young adults. Reliability analyses according to muscle sympathetic burst size, burst pattern, and nonburst response were less consistent. Results were similar when using diastolic or mean arterial pressure in the transduction calculation. These findings suggest that the signal-averaging technique can be used with confidence to investigate sympathetic transduction to blood pressure in humans across time.
Assuntos
Músculo Esquelético , Sistema Nervoso Simpático , Adulto Jovem , Humanos , Pressão Sanguínea/fisiologia , Reprodutibilidade dos Testes , Músculo Esquelético/fisiologia , Sistema Nervoso Simpático/fisiologia , Frequência Cardíaca/fisiologiaRESUMO
The blood pressure-lowering effect of aerobic training is preceded by improving cardiovascular autonomic control. We previously demonstrated that aerobic training conducted in the evening (ET) induces a greater decrease in blood pressure than morning training (MT). To study whether the greater blood pressure decrease after ET occurs through better cardiovascular autonomic regulation, this study aimed to compare MT versus ET on muscle sympathetic nerve activity (MSNA) and baroreflex sensitivity (BRS) in treated patients with hypertension. Elderly patients treated for hypertension were randomly allocated into MT (n = 12, 07.00-10.00 h) or ET (n = 11, 17.00-20.00 h) groups. Both groups trained for 10 weeks, 3 times/week, cycling for 45 min at moderate intensity. Beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and MSNA (microneurography) were assessed at the initial and final phases of the study at baseline and during sequential bolus infusions of sodium nitroprusside and phenylephrine (modified-Oxford technique) to evaluate cardiac and sympathetic BRS. Mean blood pressure decreased significantly after ET but not after MT (-9 ± 11 vs. -1 ± 8 mmHg, P = 0.042). MSNA decreased significantly only after ET with no change after MT (-12 ± 5 vs. -3 ± 7 bursts/100 heart beats, P = 0.013). Sympathetic BRS improved after ET but not after MT (-0.8 ± 0.7 vs. 0.0 ± 0.8 bursts/100 heart beats/mmHg, P = 0.052). Cardiac BRS improved similarly in both groups (ET: +1.7 ± 1.8 vs. MT: +1.4 ± 1.9 ms/mmHg, Pphase ≤ 0.001). In elderly patients treated for hypertension, only ET decreased mean blood pressure and MSNA and improved sympathetic BRS. These findings revealed that the sympathetic nervous system has a key role in ET's superiority to MT in blood pressure-lowering effect. KEY POINTS: Reducing muscle nerve sympathetic activity and increasing sympathetic baroreflex sensitivity plays a key role in promoting the greater blood pressure reduction observed with evening training. These findings indicated that simply changing the timing of exercise training may offer additional benefits beyond antihypertensive medications, such as protection against sympathetic overdrive and loss of baroreflex sensitivity, independent markers of mortality. Our new findings also suggest new avenues of investigation, such as the possibility that evening aerobic training may be beneficial in other clinical conditions with sympathetic overdrive, such as congestive heart failure and hypertrophic cardiomyopathy.
Assuntos
Sistema Cardiovascular , Hipertensão , Humanos , Idoso , Barorreflexo/fisiologia , Hipertensão/terapia , Pressão Sanguínea/fisiologia , Coração , Sistema Nervoso Simpático/fisiologia , Frequência Cardíaca/fisiologia , Músculo EsqueléticoRESUMO
PURPOSE: We sought to investigate the sympathetic mechanism controlling coronary circulation during trigeminal nerve stimulation in healthy women. METHODS: The protocol consisted of 3 min of trigeminal nerve stimulation (TGS) with cold stimuli to the face, in two conditions: (1) control and ß-blockade (oral propranolol), and (2) control and α-blockade (oral prazosin). RESULTS: Thirty-one healthy young subjects (women: n = 13; men: n = 18) participated in the study. By design, TGS decreased heart rate (HR), and increased blood pressure (BP) and cardiac output (CO). Before the ß-blockade coronary blood velocity (CBV-Δ1.4 ± 1.3 cm s-1) increased along with the decrease of coronary vascular conductance index (CVCi-Δ-0.04 ± 0.04 cm s-1 mmHg-1) during TGS and the ß-blockade abolished the CBV increase and a further decrease of CVCi was observed with TGS (Δ-0.06 ± 0.07 cm s-1 mmHg-1). During the α-blockade condition before the blockade, the CBV increased (Δ0.93 ± 1.48 cm s-1) along with the decrease of CVCi (Δ-0.05 ± 1.12 cm s-1 mmHg-1) during TGS, after the α-blockade CBV (Δ0.98 ± cm s-1) and CVCi (Δ-0.03 ± 0.06 cm s-1 mmHg-1) response to TGS did not change. CONCLUSION: Coronary circulation increases during sympathetic stimulation even with a decrease in heart rate.
Assuntos
Circulação Coronária , Vasos Coronários , Masculino , Humanos , Feminino , Pressão Sanguínea/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Coronária/fisiologia , Vasos Coronários/inervação , Frequência Cardíaca/fisiologia , Nervo Trigêmeo , Sistema Nervoso Simpático/fisiologiaRESUMO
We tested the hypothesis that third ventricular (3V) injections of angiotensin 1-7 (Ang 1-7) increases thermogenesis in brown adipose tissue (BAT), and whether the Mas receptor mediates this response. First, in male Siberian hamsters (n = 18), we evaluated the effect of Ang 1-7 in the interscapular BAT (IBAT) temperature and, using selective Mas receptor antagonist A-779, the role of Mas receptor in this response. Each animal received 3V injections (200 nL), with 48 h intervals: saline; Ang 1-7 (0.03, 0.3, 3, and 30 nmol); A-779 (3 nmol); and Ang 1-7 (0.3 nmol) + A-779 (3 nmol). IBAT temperature increased after 0.3 nmol Ang 1-7 compared with Ang 1-7 + A-779 at 20, 30, and 60 min. Also, 0.3 nmol Ang 1-7 increased IBAT temperature at 10 and 20 min, and decreased at 60 min compared with pretreatment. IBAT temperature decreased after A-779 at 60 min and after Ang 1-7 + A-779 at 30 and 60 min compared with the respective pretreatment. A-779 and Ang 1-7 + A-779 decreased core temperature at 60 min compared with 10 min. Then, we evaluated blood and tissue Ang 1-7 levels, and the expression of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) in IBAT. Male Siberian hamsters (n = 36) were killed 10 min after one of the injections. No changes were observed in blood glucose, serum and IBAT Ang 1-7 levels, and ATGL. Ang 1-7 (0.3 nmol) increased p-HSL expression compared with A-779 and increased p-HSL/HSL ration compared with other injections. Ang 1-7 and Mas receptor immunoreactive cells were found in brain regions that coincide with the sympathetic nerves outflow to BAT. In conclusion, 3V injection of Ang 1-7 induced thermogenesis in IBAT in a Mas receptor-dependent manner.
Assuntos
Tecido Adiposo Marrom , Phodopus , Cricetinae , Animais , Masculino , Tecido Adiposo Marrom/metabolismo , Termogênese/fisiologia , Sistema Nervoso Simpático/fisiologiaRESUMO
PURPOSE: We investigate the impact of menopause on cardiovascular adjustments to the cold pressor test (CPT) and the role of the α1-adrenergic receptor. METHODS: Ten young women (YW) and nine postmenopausal women (MW) underwent 1 min of CPT in control and α1-blockade conditions (0.03 mgâ§kg-1 of oral prazosin). RESULTS: CPT increased heart rate (HR) (YW: ∆20 ± 3 bpm; MW: ∆13 ± 2 bpm) and stroke volume (SV; YW: ∆15 ± 8 ml; MW: ∆9 ± 6 ml; p = 0.01 for time) and evoked a greater increase in cardiac output (CO) in YW (YW: ∆2.1 ± 0.2 lâ§m-1; MW: ∆1.3 ± 0.5 lâ§m-1; p = 0.01). α1-Blockade increased baseline HR and did not change HR, SV, and CO responses to CPT. MW presented an exaggerated systolic blood pressure (BP) response (YW: ∆38 ± 9 mmHg; MW: ∆56 ± 24 mmHg; p = 0.03). The α1-blockade did not change baseline BP while blunting its response. Total vascular resistance (TVR) was similar between groups at baseline and increased during CPT only in MW (YW: ∆2.3 ± 1.4 mmHgâ§L-1â§min; MW:∆6.8 ± 5.9 mmHgâ§L-1â§min). Under α1-blockade, the TVR increase during CPT was attenuated in MW and abolished in YW (YW: ∆0.3 ± 1.2 mmHgâ§L-1â§min and MW: ∆3.0 ± 2.0 mmHgâ§L-1â§min). CPT did not change femoral vascular conductance (FVC) in either group before the blockade (YW: ∆-0.3 ± 4.0 mlâ§min-1â§mmHg-1; MW: ∆-0.2 ± 0.8 mlâ§min-1â§mmHg-1); however, FVC tended to increase in young women (YW: ∆1.3 ± 1.0 mlâ§min-1â§mmHg-1; MW: ∆0.1 ± 1.5 mlâ§min-1â§mmHg-1; p = 0.06) after the α1-blockade. CONCLUSION: In postmenopausal women, the cardiac ability to adjust to CPT is blunted and α1-adrenergic receptor stimulation is important for the increase in stroke volume. In addition, the peripheral effect of α1-adrenergic receptor stimulation seems to be increased in postmenopausal women.
Assuntos
Sistema Cardiovascular , Sistema Nervoso Simpático , Adrenérgicos/farmacologia , Pressão Sanguínea/fisiologia , Temperatura Baixa , Feminino , Frequência Cardíaca/fisiologia , Humanos , Pós-Menopausa , Sistema Nervoso Simpático/fisiologiaRESUMO
NEW FINDINGS: What is the central question of this study? What is the role of ß- and α-adrenergic receptors in the control of the coronary circulation during handgrip exercise and isolated muscle metaboreflex activation in humans? What is the main finding and its importance? ß-Adrenergic receptor, but not α-adrenergic receptor, blockade significantly blunted the increases in coronary blood velocity observed during handgrip. Coronary blood velocity was unchanged from baseline during isolated muscle metaboreflex activation. This highlights the important role of ß-adrenergic receptors in the coronary circulation during handgrip in humans, and the more limited involvement of the α-adrenergic receptors. ABSTRACT: We sought to investigate the role of ß- and α-adrenergic receptors in coronary circulation during static handgrip exercise and isolated muscle metaboreflex activation in humans. Seventeen healthy young men underwent two experimental sessions, consisting of 3 min of static handgrip exercise at a target force of 40% maximum voluntary force (not achieved for the full 3 min), and 3 min of metaboreflex activation (post-exercise ischaemia) in two conditions: (1) control and ß-blockade (oral propranolol), and (2) control and α-blockade (oral prazosin). In both sessions, coronary blood velocity (CBV, echocardiography) was increased during handgrip (Δ8.0 ± 7.4 cm s-1 ) but unchanged with metaboreflex activation (Δ2.5 ± 3.2 cm s-1 ) under control conditions. ß-Blockade abolished the increase in CBV during handgrip, while CBV was unchanged from control with α-blockade. Cardiac work, estimated from rate pressure product (RPP; systolic blood pressure multiplied by heart rate), increased during handgrip and metaboreflex in control conditions in both sessions. ß-Blockade reduced RPP responses to handgrip and metaboreflex, whereas α-blockade increased RPP, but the responses to handgrip and metaboreflex were unchanged. CBV and RPP were only significantly correlated during handgrip under control (r = 0.71, P < 0.01) and ß-blockade (r = 0.54, P = 0.03) conditions, and the slope of this relationship was unaltered with ß-blockade. Collectively, these findings indicate that ß-adrenergic receptors play the primary role to the increase of coronary circulation during handgrip exercise, but CBV is unchanged with metaboreflex activation, while α-adrenergic receptor stimulation seems to exert no effect in the control of the coronary circulation during handgrip exercise and isolated muscle metaboreflex activation in humans.
Assuntos
Força da Mão , Músculo Esquelético , Pressão Sanguínea/fisiologia , Circulação Coronária , Exercício Físico/fisiologia , Força da Mão/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Músculo Esquelético/fisiologia , Sistema Nervoso Simpático/fisiologiaRESUMO
Spinal cord neurons contribute to elevated sympathetic vasomotor activity in renovascular hypertension (2K1C), particularly, increased actions of angiotensin II. However, the origin of these spinal angiotensinergic inputs remains unclear. The present study aimed to investigate the role of spinal angiotensin II type 1 receptor (AT1) receptors in the sympathoexcitatory responses evoked by the activation of the rostral ventrolateral medulla (RVLM) in control and 2K1C Goldblatt rats. Hypertension was induced by clipping of the left renal artery. After 6 weeks, a catheter (PE-10) filled with losartan was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anesthetized rats. The effects of glutamate microinjection into the RVLM on blood pressure (BP), heart rate (HR), and renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively) were evaluated in the presence or absence of spinal AT1 blockade. Tachycardic, pressor, and renal sympathoexcitatory effects caused by RVLM activation were significantly blunted by losartan in 2K1C rats, but not in control rats. However, no differences were found in the gene expression of angiotensin-converting enzyme, angiotensinogen, and renin in the spinal cord segments between the groups. In conclusion, acute sympathoexcitation induced by RVLM activation is dependent on the spinal AT1 receptor in Goldblatt, but not in control, rats. The involvement of other central cardiovascular nuclei in spinal angiotensinergic actions, as well as the source of angiotensin II, remains to be determined in the Goldblatt model.
Assuntos
Hipertensão/fisiopatologia , Rim/inervação , Bulbo/fisiologia , Receptor Tipo 1 de Angiotensina/fisiologia , Medula Espinal/metabolismo , Sistema Nervoso Simpático/fisiologia , Animais , Hipertensão/metabolismo , Masculino , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismoRESUMO
Experiments aimed to evaluate the tissue distribution of Mas-related G protein-coupled receptor D (MrgD) revealed the presence of immunoreactivity for the MrgD protein in the rostral insular cortex (rIC), an important area for autonomic and cardiovascular control. To investigate the relevance of this finding, we evaluated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were recorded in urethane anesthetized rats. Unilateral microinjection of equimolar doses of alamandine (40 pmol/100 nL), angiotensin-(1-7), angiotensin II, angiotensin A, and Mas/MrgD antagonist d-Pro7-Ang-1-7 (50 pmol/100 nL), Mas antagonist A779 (100 pmol/100 nL), or vehicle (0.9% NaCl) were made in different rats (n = 4-6/group) into rIC. To verify the specificity of the region, a microinjection of alamandine was also performed into intermediate insular cortex (iIC). Microinjection of alamandine in rIC produced an increase in MAP (Δ = 15 ± 2 mmHg), HR (Δ = 36 ± 4 beats/min), and RSNA (Δ = 31 ± 4%), but was without effects at iIC. Strikingly, an equimolar dose of angiotensin-(1-7) at rIC did not produce any change in MAP, HR, and RSNA. Angiotensin II and angiotensin A produced only minor effects. Alamandine effects were not altered by A-779, a Mas antagonist, but were completely blocked by the Mas/MrgD antagonist d-Pro7-Ang-(1-7). Therefore, we have identified a brain region in which alamandine/MrgD receptor but not angiotensin-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to angiotensin-(1-7) in the brain.
Assuntos
Angiotensina I/farmacologia , Pressão Arterial/efeitos dos fármacos , Sistema Cardiovascular/inervação , Córtex Cerebral/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Rim/inervação , Proteínas do Tecido Nervoso/agonistas , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Córtex Cerebral/fisiologia , Ligantes , Masculino , Microinjeções , Proteínas do Tecido Nervoso/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/agonistas , Proteínas Proto-Oncogênicas/metabolismo , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/metabolismo , Sistema Nervoso Simpático/fisiologiaRESUMO
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.