RESUMO
Aortic baroreceptor afferents act as targets for blood pressure control in hypertension.
Assuntos
Aorta , Barorreflexo , Pressão Sanguínea , Hipertensão , Pressorreceptores , Animais , Humanos , Aorta/inervação , Hipertensão/fisiopatologia , Hipertensão/terapia , Pressorreceptores/fisiopatologia , Ratos , Estimulação ElétricaRESUMO
Baroreceptors are nerve endings located in the adventitia of the carotid sinus and aortic arch. They act as a mechanoelectrical transducer that can sense the tension stimulation exerted on the blood vessel wall by the rise in blood pressure and transduce the mechanical force into discharge of the nerve endings. However, the molecular identity of mechanical signal transduction from the vessel wall to the baroreceptor is not clear. We discovered that exogenous integrin ligands, such as RGD, IKVAV, YIGSR, PHSRN, and KNEED, could restrain pressure-dependent discharge of the aortic nerve in a dose-dependent and reversible manner. Perfusion of RGD at the baroreceptor site in vivo can block the baroreceptor reflex. An immunohistochemistry study showed the binding of exogenous RGD to the nerve endings under the adventitia of the rat aortic arch, which may competitively block the binding of integrins to ligand motifs in extracellular matrix. These findings suggest that connection of integrins with extracellular matrix plays an important role in the mechanical coupling process between vessel walls and arterial baroreceptors.
Assuntos
Mecanotransdução Celular , Pressorreceptores , Ratos , Animais , Pressorreceptores/fisiologia , Aorta/inervação , ArtériasRESUMO
Arterial baroreceptors (BRs) play a vital role in the regulation of the cardiopulmonary system. What is known about how these sensors operate at the subcellular level is limited, however. Until recently, one afferent axon was considered to be connected to a single baroreceptor (one-sensor theory). However, in the lung, a single airway mechanosensory unit is now known to house many sensors (multiple-sensor theory). Here we tested the hypothesis that multiple-sensor theory also operates in BR units, using both morphological and electrophysiological approaches in rabbit aortic arch (in whole mount) labeled with Na+/K+-ATPase, as well as myelin basic protein antibodies, and examined microscopically. Sensory structures presented in compact clusters, similar to bunches of grapes. Sensory terminals, like those in the airways, formed leaf-like or knob-like expansions. That is, a single myelinated axon connected with multiple sensors forming a network. We also recorded single-unit activities from aortic baroreceptors in the depressor nerve in anesthetized rabbits and examined the unit response to a bolus intravenous injection of phenylephrine. Unit activity increased progressively as blood pressure (BP) increased. Five of eleven units abruptly changed their discharge pattern to a lower activity level after BP attained a plateau for a minute or two (when BP was maintained at the high level). These findings clearly show that the high discharge baroreceptor deactivates after over-excitation and unit activity falls to a low discharge sensor. In conclusion, our morphological and physiological data support the hypothesis that multiple-sensory theory can be applied to BR units.
Assuntos
Aorta Torácica/fisiopatologia , Aorta/inervação , Pressorreceptores/fisiologia , Animais , Anticorpos/química , Aorta/fisiopatologia , Axônios/fisiologia , Pressão Sanguínea , Eletrofisiologia , Pulmão/fisiologia , Masculino , Modelos Neurológicos , Proteína Básica da Mielina/metabolismo , Fenilefrina , Coelhos , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Changes in the arterial baroreflex arc contribute to elevated sympathetic outflow and altered reflex control of blood pressure with human aging. Using ultrasound and sympathetic microneurography (muscle sympathetic nerve activity, MSNA) we investigated the relationships between aortic and carotid artery wall tension (indices of baroreceptor activation) and the vascular sympathetic baroreflex operating point (OP; MSNA burst incidence) in healthy, normotensive young (n = 27, 23 ± 3 yr) and middle-aged men (n = 22, 55 ± 4 yr). In young men, the OP was positively related to the magnitude and rate of unloading and time spent unloaded in the aortic artery (r = 0.56, 0.65, and 0.51, P = 0.02, 0.003, and 0.03), but not related to the magnitude or rate of unloading or time spent unloaded in the carotid artery (r = -0.32, -0.07, and 0.06, P = 0.25, 0.81, and 0.85). In contrast, in middle-aged men, the OP was not related to either the magnitude or rate of unloading or time spent unloaded in the aortic (r = 0.22, 0.21, and 0.27, P = 0.41, 0.43, and 0.31) or carotid artery (r = 0.06, 0.28, and -0.01; P = 0.48, 0.25, and 0.98). In conclusion, in young men, aortic unloading mechanics may play a role in determining the vascular sympathetic baroreflex OP. In contrast, in middle-aged men, barosensory vessel unloading mechanics do not appear to determine the vascular sympathetic baroreflex OP and, therefore, do not contribute to age-related arterial baroreflex resetting and increased resting MSNA.NEW & NOTEWORTHY We assessed the influence of barosensory vessel mechanics (magnitude and rate of unloading and time spent unloaded) as a surrogate for baroreceptor unloading. In young men, aortic unloading mechanics are important in regulating the operating point of the vascular sympathetic baroreflex, whereas in middle-aged men, these arterial mechanics do not influence this operating point. The age-related increase in resting muscle sympathetic nerve activity does not appear to be driven by altered baroreceptor input from stiffer barosensory vessels.
Assuntos
Envelhecimento , Aorta/inervação , Pressão Arterial , Barorreflexo , Artérias Carótidas/inervação , Músculo Esquelético/inervação , Pressorreceptores/fisiologia , Adulto , Fatores Etários , Aorta/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Frequência Cardíaca , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a difficult disease with high morbidity and mortality rates and lacks an effective treatment. Here, we report the therapeutic effect of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), on hypertension + hyperlipidemia-induced HFpEF in a pig model. METHODS: HFpEF pigs were established by infusing a combination of deoxycorticosterone acetate (DOCA) and angiotensin II (Ang II), and Western diet (WD) feeding for 18 weeks. In the 9th week, half of the HFpEF pigs were randomly assigned to receive additional dapagliflozin treatment (10 mg/day) by oral gavage daily for the next 9 weeks. Blood pressure, lipid levels, echocardiography and cardiac hemodynamics for cardiac structural and functional changes, as well as epinephrine and norepinephrine concentrations in the plasma and tissues were measured. After sacrifice, cardiac fibrosis, the distribution of tyrosine hydroxylase (TH), inflammatory factors (IL-6 and TNF-α) and NO-cGMP-PKG pathway activity in the cardiovascular system were also determined. RESULTS: Blood pressure, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) were markedly increased in HFpEF pigs, but only blood pressure was significantly decreased after 9 weeks of dapagliflozin treatment. By echocardiographic and hemodynamic assessment, dapagliflozin significantly attenuated heart concentric remodeling in HFpEF pigs, but failed to improve diastolic function and compliance with the left ventricle (LV). In the dapagliflozin treatment group, TH expression and norepinephrine concentration in the aorta were strongly mitigated compared to that in the HFpEF group. Moreover, inflammatory cytokines such as IL-6 and TNF-α in aortic tissue were markedly elevated in HFpEF pigs and inhibited by dapagliflozin. Furthermore, the reduced expression of eNOS and the PKG-1 protein and the cGMP content in the aortas of HFpEF pigs were significantly restored after 9 weeks of dapagliflozin treatment. CONCLUSION: 9 weeks of dapagliflozin treatment decreases hypertension and reverses LV concentric remodeling in HFpEF pigs partly by restraining sympathetic tone in the aorta, leading to inhibition of the inflammatory response and NO-cGMP-PKG pathway activation.
Assuntos
Aorta/inervação , Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , GMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Fibrose , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Mediadores da Inflamação/metabolismo , Lipídeos/sangue , Óxido Nítrico/metabolismo , Norepinefrina/metabolismo , Sus scrofa , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologiaRESUMO
Combined retrograde tracing and double-labelling immunofluorescence were used to investigate the distribution and chemical coding of neurons in aorticoerenal (ARG) and testicular (TG) ganglia supplying the urinary bladder apex (UBA) in the juvenile male pig (n=4, 12 kg. body weight). Retrograde fluorescent tracer Fast Blue (FB) was injected into the wall of the bladder apex under pentobarbital anesthesia. After three weeks all the pigs were deeply anesthetized and transcardially perfused with 4% buffered paraformaldehyde. TG and ARG were collected and processed for double-labelling immunofluorescence. The presence of tyrosine hydroxylase (TH) or dopamine beta-hydroxylase (DBH), neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL), nitric oxide synthase (NOS) and vesicular acetylcholine transporter (VAChT) were investigated. The cryostat sections were examined with a Zeiss LSM 710 confocal microscope equipped with adequate filter blocks. The TG and ARG were found to contain many FB-positive neurons projecting to the UBA (UBA-PN). The UBA-PN were distributed in both TG and ARG. The majority were found in the left ganglia, mostly in TG. Immunohistochemistry disclosed that the vast majority of UBA-PN were noradrenergic (TH- and/or DBH-positive). Many noradrenergic neurons also contained immunoreactivity to NPY, SOM or GAL. Most of the UBA-PN were supplied with varicose VAChT-, or NOS- IR (immunoreactive) nerve fibres. This study has revealed a relatively large population of differently coded ARG and TG neurons projecting to the porcine urinary bladder. As judged from their neurochemical organization these nerve cells constitute an important element of the complex neuro-endocrine system involved in the regulation of the porcine urogenital organ function.
Assuntos
Aorta/inervação , Gânglios/citologia , Rim/inervação , Suínos , Testículo/inervação , Bexiga Urinária/inervação , Animais , Gânglios/fisiologia , MasculinoRESUMO
OBJECTIVES: This study sought to develop a method to assess renal sympathetic nerve function through localization and pacing of aorticorenal ganglia (ARG). BACKGROUND: Transcatheter renal denervation procedures often fail to produce complete renal denervation because of the lack of a physiological procedural endpoint. METHODS: High-frequency pacing was performed in the inferior vena cava and aorta in sheep (n = 19) to identify ARG pace-capture sites. Group A (n = 5) underwent injection at the ARG pace-capture site for histological verification, group B (n = 6) underwent unilateral irrigated radiofrequency ablation of ARG pace-capture sites and assessment of renal innervation at 1 week post-procedure; and group C (n = 8) underwent ARG pacing before and 2 to 3 weeks after unilateral microwave renal denervation. RESULTS: ARG pace-capture responses were observed at paired discrete sites above the ipsilateral renal artery eliciting a change in mean arterial blood pressure of 22.2 (interquartile range [IQR]: 15.5 to 34.3 mm Hg; p < 0.001) with concurrent ipsilateral renal arterial vasoconstriction, change in main renal artery diameter of -0.42 mm (IQR: -0.64 to -0.24 mm; p < 0.0001), and without consistent contralateral renal vasoconstriction. Sympathetic ganglionic tissue was observed at ARG pace-capture sites, and ganglion ablation led to significant ipsilateral renal denervation. Circumferential renal denervation resulted in immediate and sustained abolition of ARP pacing-induced renal vasoconstriction and significant ipsilateral renal denervation. CONCLUSIONS: Transvascular ARG pace-capture is feasible and recognized by concurrent hypertensive and ipsilateral renal arterial vasoconstrictive responses. Abolition of ARG pacing-induced vasoconstriction may indicate successful renal sympathetic denervation and serve as a physiological procedural endpoint to guide transcatheter renal denervation.
Assuntos
Aorta/inervação , Ablação por Cateter , Determinação de Ponto Final , Gânglios Simpáticos/fisiologia , Rim/irrigação sanguínea , Micro-Ondas , Artéria Renal/inervação , Simpatectomia , Potenciais de Ação , Animais , Pressão Sanguínea , Ablação por Cateter/efeitos adversos , Estimulação Elétrica , Masculino , Micro-Ondas/efeitos adversos , Carneiro Doméstico , Fatores de Tempo , VasoconstriçãoRESUMO
BACKGROUND: Age-associated arterial stiffening may be the result of greater tonic sympathetic nerve activity. However, age-associated changes in central artery responsiveness to sympathoexcitatory stimuli are understudied. Therefore, we examined changes in central artery stiffness and wave reflection in response to sympathoexcitatory stimuli in young and older adults. METHODS: Fourteen young (25 ± 4 years) and 15 older (68 ± 4 years) subjects completed 3 minutes of the cold pressor test (CPT) and lower-body negative pressure (LBNP) separated by 15 minutes. Carotid-femoral pulse wave velocity (cfPWV), central augmentation pressure (cAP), and augmentation index (AIx) were measured in duplicate during rest and the final minute of each perturbation. RESULTS: Young subjects had lower baseline cfPWV, cAP, and AIx than older subjects (P < 0.05 for all). During the CPT mean arterial pressure (MAP), cfPWV, cAP, and AIx increased in both groups (P < 0.05 for all); however, changes (Δ) in MAP (18 ± 7 vs. 9 ± 5 mm Hg), cfPWV (1.3 ± 0.7 vs. 0.6 ± 0.9 m/s), cAP (4 ± 2 vs. 6 ± 3 mm Hg), and AIx (18 ± 9% vs. 7 ± 4%) were greater in young vs. older subjects, respectively (P < 0.05 for all). With MAP as a covariate, cfPWV, cAP, and AIx responses to the CPT were no longer significantly different between groups. During LBNP, changes in MAP (-1 ± 3 vs. -3 ± 5 mm Hg), cfPWV (0.5 ± 0.3 vs. 0.5 ± 0.7 m/s), cAP (-2 ± 2 vs. -2 ± 3 mm Hg), and AIx (-7 ± 7% vs. -3 ± 6%) were similar between young and older groups, respectively (P > 0.05 for all). CONCLUSIONS: Collectively, our data suggest the sympathetic nervous system may directly modulate central hemodynamics and that age-associated differences in central artery responsiveness to sympathoexcitatory stimuli are largely attributable to differential blood pressure responses.
Assuntos
Aorta/inervação , Pressão Arterial , Sistema Nervoso Simpático/fisiologia , Rigidez Vascular , Adulto , Fatores Etários , Idoso , Velocidade da Onda de Pulso Carótido-Femoral , Temperatura Baixa , Resposta ao Choque Frio , Feminino , Humanos , Pressão Negativa da Região Corporal Inferior , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Baroreflex dysfunction is a diffuse chronic condition that is expected to be followed by a profound loss of organization of BP and HR variability. Nevertheless, long-term effects of baroreflex withdrawal are still debated. Aim of our work was to study BP and HR changes long term after sino-aortic denervation (SAD). Inter-beat-interval (IBI) and intra-arterial BP were recorded beat-by-beat in 43 Wistar-Kyoto rats (Controls, n = 33; SAD rats, n = 10). Power spectra were calculated in controls and in SAD rats within three days and at seven months from denervation. Compared to controls, chronic SAD rats showed 1) similar mean BP (control vs SAD: 95 ± 16 vs 87 ± 22 mmHg) and IBI (171 ± 22 vs 181 ± 15 ms) values, 2) dramatically higher values of BP variance (12 ± 2 vs 64 ± 2 mmHg2, p < 0.01) and of ultra- (ULF) and very-low-frequency (VLF) BP oscillations, 3) dramatically higher values of IBI variability (24 ± 2 vs 71 ± 4 ms2, p < 0.01) and of ULF-IBI oscillations that were synchronized with BP oscillations. Chronic SAD rats reveal a marked change in the pattern of cardiovascular variability characterized by the appearance of synchronized slower oscillations of BP and HR. The cardiovascular system, therefore, retains a high level of organization despite the absence of a reflex control mechanism.
Assuntos
Aorta/fisiologia , Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Nó Sinoatrial/fisiologia , Animais , Aorta/inervação , Modelos Animais , Ratos , Ratos Endogâmicos WKY , Nó Sinoatrial/inervação , Simpatectomia , Fatores de TempoRESUMO
It is well-established that baroreflex sensitivity is essential for blood pressure control, and also plays a key role in the modulation of disease-induced metabolic alterations. In order to investigate the role of the baroreflex in the cardiometabolic and inflammatory derangements promoted by fructose overload, Wistar rats underwent sinoaortic denervation (SAD) or sham surgery and were studied 90 days after receiving tap water (Den and Ctrl) or a 10% fructose solution (Fruc and Den-Fruc). All experimental groups showed marked and similar degree of baroreflex impairment compared to Ctrl. As expected, fructose overload effectively induced metabolic syndrome; however, when it was associated with SAD, several alterations were attenuated. While Fruc rats displayed increased sympathetic modulation and tone and reduced vagal modulation compared to Ctrl animals, Den-Fruc rats showed greater vagal tone and modulation when compared to the Fruc group. Moreover, the Den-Fruc group showed augmented expression of ß1 adrenergic receptors and TNF/IL-10 ratio and reduction of ß2 in the left ventricle. The increase in vagal function was correlated with improved insulin sensitivity (r2 = 0.76), and decreased abdominal fat (r2 = -0.78) and ß2 receptors (r2 = -0.85). Our results showed that: (1) chronic fructose overload induced severe baroreflex impairment, i.e. in a similar magnitude to that observed in SAD rats, which is accompanied by cardiometabolic dysfunctions; (2) the compensatory enhancement in parasympathetic function in SAD rats submitted to fructose intake may point out the possibility of use of approaches that improve vagal function as therapeutic target to attenuate fructose-induced cardiometabolic dysfunctions.
Assuntos
Barorreflexo/fisiologia , Frutose/farmacologia , Coração/fisiopatologia , Síndrome Metabólica/induzido quimicamente , Sistema Nervoso Parassimpático/fisiologia , Animais , Aorta/inervação , Pressão Sanguínea , Inflamação , Resistência à Insulina , Síndrome Metabólica/etiologia , RatosRESUMO
PURPOSE: Recently we reported the use of renal nerve stimulation (RNS) during renal denervation (RDN) procedures. RNS induced changes in blood pressure (BP) and heart rate are not fully delineated yet. We hypothesized that electrical stimulation of the sympathetic nerve tissue in the renal artery would lead to an increase in BP and vagal stimulation would cause a decrease in BP. We report the different patterns of BP and heart rate responses elicited by RNS prior to RDN. METHODS: 35 patients with drug-resistant hypertension were included. RNS was performed under general anesthesia at four sites in the right and left renal arteries, both before and immediately after RDN. RNS-induced BP and heart rate changes were monitored. RESULTS: A total of 289 RNS sites in 35 patients were analyzed. An increase in systolic BP of >10 mmHg was regarded as a positive BP response to RNS. This pattern of response was observed in 180 sites (62%). 86 RNS sites (30%) showed an indifferent response with BP changes ≤10 mmHg. At 13 sites (4.5%) RNS elicited a decrease in BP up to -8 mmHg. However, 10 RNS sites (3.5%) showed a pronounced vagal response with hypotension and sinus cycle lengths ranging between 4224-10272 milliseconds. These sites were distributed among two patients. CONCLUSION: RNS identified sympathetic and parasympathetic nerve tissue in the renal arteries. RNS can be potentially used to map nerve bundles and guide selective ablation of sympathetic nerve fibers and prevent inadvertent ablation of parasympathetic nerve tissue during RDN.
Assuntos
Aorta/inervação , Estimulação Elétrica , Rim/inervação , Simpatectomia/métodos , Idoso , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Hipertensão , Masculino , Pessoa de Meia-Idade , Artéria Renal/inervação , Artéria Renal/fisiologia , Nervo Vago/fisiologiaRESUMO
BACKGROUND: Whether the sympathetic nervous system can directly alter central aortic stiffness remains controversial, mainly because of the difficulty in experimentally augmenting peripheral vasoconstrictor activity without changing blood pressure. METHODS AND RESULTS: To address this limitation, we utilized low-level cardiopulmonary baroreflex loading and unloading shown previously to alter sympathetic outflow without evoking parallel hemodynamic modulation. Blood pressure and carotid-femoral aortic pulse wave velocity (cf-PWV) were measured in 32 healthy participants (24±2 years; women: n=15) before and during 12-minute applications of low-level lower body negative pressure; -7 mm Hg) and lower body positive pressure; +7 mm Hg), applied in a random order. Fibular nerve microneurography was used to collect muscle sympathetic nerve activity (MSNA) in a subset (n=8) to confirm peripheral sympathetic responses. During lower body negative pressure, heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were not statistically different (all P>0.05); MSNA burst frequency (+15%; P=0.007), total MSNA (+44%; P=0.006), and cf-PWV (∆+0.3±0.2 m/s; P<0.001) increased. In total, 28 (88%) of participants observed an increase in cf-PWV greater than the baseline typical error of measurement. During lower body positive pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance were not statistically different (all P>0.05), though blood pressure increased (P<0.05) and pulse pressure decreased (P=0.01); MSNA burst frequency (-4%; P=0.37), total MSNA (-7%; P=0.89), and cf-PWV (∆0.0±0.2 m/s; P=0.68) were not statistically different. CONCLUSIONS: These findings provide evidence that acute elevations in peripheral sympathetic activity can increase central aortic PWV in young participants independent of a change in distending or pulsatile blood pressure or heart rate.
Assuntos
Aorta/inervação , Pressão Arterial , Análise de Onda de Pulso , Sistema Nervoso Simpático/fisiologia , Rigidez Vascular , Adaptação Fisiológica , Adulto , Barorreflexo , Feminino , Frequência Cardíaca , Humanos , Pressão Negativa da Região Corporal Inferior , Masculino , Músculo Esquelético/inervação , Distribuição Aleatória , Adulto JovemRESUMO
We previously reported that activation of the baroreflex, a critical physiological mechanism controlling cardiovascular homeostasis, through electrical stimulation of the aortic depressor nerve attenuates joint inflammation in experimental arthritis. However, it is unknown whether baroreflex activation can control systemic inflammation. Here, we investigate whether baroreflex activation controls systemic inflammation in conscious endotoxemic rats. Animals underwent sham or electrical aortic depressor nerve stimulation initiated 10â¯min prior to a lipopolysaccharide (LPS) challenge, while inflammatory cytokine levels were measured in the blood, spleen, heart and hypothalamus 90â¯min after LPS treatment. Baroreflex activation did not affect LPS-induced levels of pro-inflammatory (tumor necrosis factor, interleukin 1ß and interleukin 6) or anti-inflammatory (interleukin 10) cytokines in the periphery (heart, spleen and blood). However, baroreflex stimulation attenuated LPS-induced levels of all these cytokines in the hypothalamus. Notably, these results indicate that the central anti-inflammatory mechanism induced by baroreflex stimulation is independent of cardiovascular alterations, since aortic depressor nerve stimulation that failed to induce hemodynamic changes was also efficient at inhibiting inflammatory cytokines in the hypothalamus. Thus, aortic depressor nerve stimulation might represent a novel therapeutic strategy for neuroprotection, modulating inflammation in the central nervous system.
Assuntos
Barorreflexo/fisiologia , Estado de Consciência , Estimulação Elétrica/métodos , Inflamação/metabolismo , Inflamação/terapia , Animais , Aorta/inervação , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Neurite do Plexo Braquial , Citocinas/metabolismo , Modelos Animais de Doenças , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos/toxicidade , Masculino , Ratos , Ratos Wistar , Baço/efeitos dos fármacos , Baço/metabolismo , Fatores de TempoRESUMO
PURPOSE OF REVIEW: Surgical removal of the baroreceptor afferents [sino-aortic denervation (SAD)] leads to a lack of inhibitory feedback to sympathetic outflow, which in turn is expected to result in a large increase in mean arterial pressure (MAP). However, few days after surgery, the sympathetic nerve activity (SNA) and MAP of SAD rats return to a range similar to that observed in control rats. In this review, we present experimental evidence suggesting that breathing contributes to control of SNA and MAP following SAD.The purpose of this review was to discuss studies exploring SNA and MAP regulation in SAD rats, highlighting the possible role of breathing in the neural mechanisms of this modulation of SNA. RECENT FINDINGS: Recent studies show that baroreceptor afferent stimulation or removal (SAD) results in changes in the respiratory pattern. Changes in the neural respiratory network and in the respiratory pattern must be considered among mechanisms involved in the modulation of the MAP after SAD.
Assuntos
Aorta/inervação , Pressão Arterial/fisiologia , Pressão Sanguínea/fisiologia , Seio Carotídeo/inervação , Pressorreceptores/fisiologia , Respiração , Animais , Aorta/fisiologia , Seio Carotídeo/fisiologia , Denervação/métodos , Hipertensão/fisiopatologia , Masculino , Rede Nervosa/fisiologia , Ratos , Sistema Nervoso Simpático/fisiologiaRESUMO
Although electrical activation of the carotid sinus baroreflex (baroreflex activation therapy) is being explored as a device therapy for resistant hypertension, possible effects on baroreflex dynamic characteristics of interaction between electrical stimulation and pressure inputs are not fully elucidated. To examine whether the electrical stimulation of the baroreceptor afferent nerve impedes normal short-term arterial pressure (AP) regulation mediated by the stimulated nerve, we electrically stimulated the right aortic depressor nerve (ADN) while estimating the baroreflex dynamic characteristics by imposing pressure inputs to the isolated baroreceptor region of the right ADN in nine anesthetized rats. A Gaussian white noise signal with a mean of 120 mmHg and standard deviation of 20 mmHg was used for the pressure perturbation. A tonic ADN stimulation (2 or 5 Hz, 10 V, 0.1-ms pulse width) decreased mean sympathetic nerve activity (367.0 ± 70.9 vs. 247.3 ± 47.2 arbitrary units, P < 0.01) and mean AP (98.4 ± 7.8 vs. 89.2 ± 4.5 mmHg, P < 0.01) during dynamic pressure perturbation. The ADN stimulation did not affect the slope of dynamic gain in the neural arc transfer function from pressure perturbation to sympathetic nerve activity (16.9 ± 1.0 vs. 14.7 ± 1.6 dB/decade, not significant). These results indicate that electrical stimulation of the baroreceptor afferent nerve does not significantly impede the dynamic characteristics of the arterial baroreflex concomitantly mediated by the stimulated nerve. Short-term AP regulation by the arterial baroreflex may be preserved during the baroreflex activation therapy.
Assuntos
Aorta/inervação , Pressão Arterial , Barorreflexo , Seio Carotídeo/inervação , Terapia por Estimulação Elétrica/métodos , Coração/inervação , Pressorreceptores/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Masculino , Mecanotransdução Celular , Ratos Endogâmicos WKY , Fatores de TempoRESUMO
Sympathetic hyperactivation, a common feature of obesity and metabolic syndrome, is a key trigger of hypertension. However, some obese subjects with autonomic imbalance present a dissociation between sympathetic activity-mediated vasoconstriction and increased blood pressure. Here, we aimed to determine in a rat model of metabolic syndrome whether the endothelium endothelial nitric oxide (NO) synthase (eNOS)-NO pathway contributes to counteract the vasopressor effect of the sympathetic system. Rats were fed a high-fat and high-sucrose (HFS) diet for 15 wk. Sympathovagal balance was evaluated by spectral analysis of heart rate variability and plasmatic catecholamine measurements. Blood pressure was measured in the presence or absence of N-nitro-l-arginine methyl ester (l-NAME) to inhibit the contribution of eNOS. Vascular reactivity was assessed on isolated aortic rings in response to α1-adrenergic agonist. The HFS diet increased sympathetic tone, which is characterized by a higher low on the high-frequency spectral power ratio and a higher plasmatic concentration of epinephrine. Despite this, no change in blood pressure was observed. Interestingly, HFS rats exhibited vascular hyporeactivity (-23.6%) to α1-adrenergic receptor stimulation that was abolished by endothelial removal or eNOS inhibition (l-NAME). In addition, eNOS phosphorylation (Ser1177) was increased in response to phenylephrine in HFS rats only. Accordingly, eNOS inhibition in vivo revealed higher blood pressure in HFS rats compared with control rats (147 vs. 126 mmHg for mean blood pressure, respectively). Restrain of adrenergic vasopressor action by endothelium eNOS is increased in HFS rats and contributes to maintained blood pressure in the physiological range. NEW & NOTEWORTHY Despite the fact that prohypertensive sympathetic nervous system activity is markedly increased in rats with early metabolic syndrome, they present with normal blood pressure. These observations appear to be explained by increased endothelial nitric oxide synthase response to adrenergic stimulation, which results in vascular hyporeactivity to α-adrenergic stimulation, and therefore blood pressure is preserved in the physiological range. Listen to this article's corresponding podcast at http://www.physiology.org/doi/10.1152/ajpheart.00217.2017 .
Assuntos
Aorta/inervação , Pressão Arterial , Endotélio Vascular/inervação , Síndrome Metabólica/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Vasoconstrição , Animais , Aorta/metabolismo , Dieta Hiperlipídica , Sacarose Alimentar , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Epinefrina/sangue , Frequência Cardíaca , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Norepinefrina/sangue , Ratos Wistar , Receptores Adrenérgicos alfa 1/metabolismo , Transdução de Sinais , Sistema Nervoso Simpático/metabolismoRESUMO
The aim of this study was to document the detailed anatomy of neural course and distribution on the anterior ascending aorta, to identify the high and low density areas of the anterior ascending aortic plexus for further understandings in cardiovascular surgery. The embalmed hearts of 42 elderly individuals were submacroscopically and microscopically examined, after excluding any that were macroscopically abnormal. With its origins in the anterior ascending aortic plexus, the right coronary plexus substantially innervated the right coronary artery, the right atrium and ventricle, and the sinus node. The intensive neural area extending from 10 mm lateral to the interatrial groove below the pericardial reflection as far as the right coronary artery opening contained almost all the right coronary plexus in 61.3% of patients, and more than 40.9% of the total nerve volume of the anterior ascending aortic plexus. Our findings suggest that the most superior and lateral area on the ascending aorta show the lowest neural density of right coronary component in the anterior ascending aortic plexus and the high density areas are invisible in right lateral field of view as seen in the right trans-axillary MICS approach.
Assuntos
Aorta/anatomia & histologia , Aorta/inervação , Vasos Coronários/anatomia & histologia , Vasos Coronários/inervação , Coração/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Coração/diagnóstico por imagem , Coração/inervação , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-IdadeRESUMO
Recent clinical trials in patients with drug-resistant hypertension indicate that electrical activation of the carotid sinus baroreflex can reduce arterial pressure (AP) for more than a year. To examine whether the electrical stimulation from one baroreflex system impedes normal short-term AP regulation via another unstimulated baroreflex system, we electrically stimulated the left aortic depressor nerve (ADN) while estimating the dynamic characteristics of the carotid sinus baroreflex in anesthetized normotensive Wistar-Kyoto (WKY; n = 8) rats and spontaneously hypertensive rats (SHR; n = 7). Isolated carotid sinus regions were perturbed for 20 min using a Gaussian white noise signal with a mean of 120 mmHg for WKY and 160 mmHg for SHR. Tonic ADN stimulation (2 Hz, 10 V, and 0.1-ms pulse width) decreased mean sympathetic nerve activity (73.4 ± 14.0 vs. 51.6 ± 11.3 arbitrary units in WKY, P = 0.012; and 248.7 ± 33.9 vs. 181.1 ± 16.6 arbitrary units in SHR, P = 0.018) and mean AP (90.8 ± 6.6 vs. 81.2 ± 5.4 mmHg in WKY, P = 0.004; and 128.6 ± 9.8 vs. 114.7 ± 10.3 mmHg in SHR, P = 0.009). The slope of dynamic gain in the neural arc transfer function from carotid sinus pressure to sympathetic nerve activity was not different between trials with and without the ADN stimulation (12.55 ± 0.93 vs. 13.03 ± 1.28 dB/decade in WKY, P = 0.542; and 17.37 ± 1.01 vs. 17.47 ± 1.64 dB/decade in SHR, P = 0.946). These results indicate that the tonic ADN stimulation does not significantly modify the dynamic characteristics of the carotid sinus baroreflex.
Assuntos
Aorta/fisiopatologia , Barorreflexo , Pressão Sanguínea , Seio Carotídeo/fisiopatologia , Hipertensão/fisiopatologia , Nervo Vago/fisiopatologia , Animais , Aorta/inervação , Estimulação Elétrica/métodos , Retroalimentação Fisiológica , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
OBJECTIVE: The sympathetic nervous system (SNS) can undergo dramatic structural plasticity in response to behavioral factors and/or the presence of disease, leading to SNS hyperinnervation of peripheral tissues. The SNS has been proposed as an important mediator between stressful behavior and the progression of atherosclerosis in the vasculature. The present study examined whether structural remodeling of the SNS occurs in the vasculature in a genetically hyperlipidemic animal model of atherosclerosis, the Watanabe heritable hyperlipidemic rabbit (WHHL; relative to normolipidemic New Zealand white rabbits [NZW]), and whether SNS plasticity is driven by the progression of disease and/or by stressful social behavior. METHODS: WHHL and NZW rabbits were assigned to an unstable or stable social environment for 4 months. Aortic atherosclerosis was assessed and SNS aortic innervation quantified using immunofluorescent microscopy. RESULTS: Numerous SNS varicosities were observed throughout the aorta in WHHLs and NZWs, extending into the vascular media and intima, an innervation pattern not previously reported. WHHLs exhibited significantly greater innervation than NZWs (F(1,41) = 55.3, p < .001), with extensive innervation of the atherosclerotic neointima. The innervation density was highly correlated with the extent of disease in the WHHLs (r(21) = 0.855, p < .001). Social environment did not influence innervation in NZWs (aortic arch: p = .078, thoracic aorta: p = .34) or WHHLs (arch: p = .97, thoracic: p = .61). CONCLUSIONS: The findings suggest that hyperinnervation is driven largely by the progression of disease rather than social environment. SNS innervation patterns observed in atherosclerotic human and mouse aortas were consistent with the rabbit, suggesting that SNS hyperinnervation of the diseased vessel wall is a general feature across mammalian species.
Assuntos
Aorta/diagnóstico por imagem , Aorta/inervação , Doenças da Aorta/diagnóstico por imagem , Aterosclerose/diagnóstico por imagem , Meio Social , Estresse Psicológico/complicações , Sistema Nervoso Simpático/diagnóstico por imagem , Animais , Doenças da Aorta/etiologia , Aterosclerose/etiologia , Modelos Animais de Doenças , Progressão da Doença , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , CoelhosRESUMO
Central (aortic) blood pressure, arterial stiffness, and sympathetic nerve activity increase with age in women. However, it is unknown if the age-related increase in sympathetic activity influences aortic hemodynamics and carotid-femoral pulse wave velocity (cfPWV), an index of central aortic stiffness. The goal of this study was to determine if aortic hemodynamics and cfPWV are directly influenced by sympathetic nerve activity by measuring aortic hemodynamics, cfPWV, and muscle sympathetic nerve activity (MSNA) in women before and during autonomic ganglionic blockade with trimethaphan camsylate. We studied 12 young premenopausal (23 ± 4 yr) and 12 older postmenopausal (57 ± 3 yr) women. These women did not differ in body mass index or mean arterial pressure (P > 0.05 for both). At baseline, postmenopausal women had higher aortic pulse pressure, augmented pressure, augmentation index adjusted for a heart rate of 75 beats/min, wasted left ventricular pressure energy, and cfPWV than young women (P < 0.05). During ganglionic blockade, postmenopausal women had a greater decrease in these variables in comparison to young women (P < 0.05). Additionally, baseline MSNA was negatively correlated with the reductions in aortic pulse pressure, augmented pressure, and wasted left ventricular pressure energy during ganglionic blockade in postmenopausal women (P < 0.05) but not young women. Baseline MSNA was not correlated with the changes in augmentation index adjusted for a heart rate of 75 beats/min or cfPWV in either group (P > 0.05 for all). Our results suggest that some aortic hemodynamic parameters are influenced by sympathetic activity to a greater extent in older postmenopausal women than in young premenopausal women.NEW & NOTEWORTHY Autonomic ganglionic blockade results in significant decreases in multiple aortic pulse wave characteristics (e.g., augmented pressure) and central pulse wave velocity in older postmenopausal women but not in young premenopausal women. Certain aortic pulse wave parameters are negatively influenced by sympathetic activity to a greater extent in older postmenopausal women.