Benedito H Machado

Benedito H Machado
University of São Paulo | USP

About

224
Publications
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4,898
Citations
Citations since 2016
37 Research Items
1973 Citations
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20162017201820192020202120220100200300
20162017201820192020202120220100200300

Publications

Publications (224)
Article
Full-text available
The autonomic profile of mice submitted to sustained hypoxia (SH) was not yet fully evaluated. Herein, we characterized the cardiovascular and autonomic profile of conscious freely moving mice submitted to SH using two sequential experimental protocols to evaluate the parasympathetic and sympathetic tone to the heart and the sympathetic tone to the...
Article
Full-text available
Twenty-five years ago, a new physiological preparation called the working heart-brainstem preparation (WHBP) was introduced with the claim it would provide a new platform allowing studies not possible before in cardiovascular, neuroendocrine, autonomic and respiratory research. Herein, we review some of the progress made with the WHBP, some advanta...
Article
Key points: Hypercapnia induces active expiration in rats and the recruitment of a specific population of expiratory neurones in the lateral parafacial (pFL ) region. Post-synaptic GABAergic and glycinergic inhibition both suppress the activity of glutamatergic pFL neurones during inspiratory and expiratory phases in normocapnia. Hypercapnia reduc...
Article
New findings: What is the central question of this study? Do mice submitted to sustained hypoxia present autonomic and respiratory changes similarly to rats? What is the main finding and its importance? Arterial pressure in the normal range, reduced baseline heart rate and tachypnoea were observed in behaving sustained hypoxia mice. Recordings in...
Article
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The two senior authors of this article would like to retract it after having conducted a thorough review of all original recordings and previous data analyses and found that the data were not a...
Article
Short-term sustained hypoxia (SH) elicits active expiration, augmented late-expiratory (late-E) sympathetic activity, increased arterial pressure and ventilation, and amplified sympathetic and abdominal expiratory responses to chemoreflex activation in rats of the Wistar-Ribeirão Preto (WRP) strain. Herein, we investigated whether SH can differenti...
Article
Full-text available
New findings: What is the central question of this study? Adrenomedullin in the rostral ventrolateral medulla (RVLM) increases sympathetic activity. Given that adrenomedullin is released during hypoxia, we explored its antagonism and agonism in the RVLM after chronic intermittent hypoxia (CIH) exposure. What is the main finding and its importance?...
Article
Full-text available
New findings: What is the central question of this study? Chronic intermittent hypoxia (CIH) causes increased arterial pressure (AP), sympathetic overactivity, and changes in expiratory modulation of sympathetic activity. However, changes in short-term sleep-wake cycle pattern after CIH and their potential impact on cardiorespiratory parameters ha...
Article
Key points: Rats subjected to sustained hypoxia (SH) present increases in arterial pressure (AP) and in glutamatergic transmission in the nucleus tractus solitarius (NTS) neurons sending projections to ventrolateral medulla (VLM). Treatment with minocycline, a microglial inhibitor, attenuated the increase in AP in response to SH. The increase in t...
Article
Sustained hypoxia (SH) activates chemoreceptors to produce cardiovascular and respiratory responses to bring the PaO 2 back to the physiological range. We evaluated the effect of SH (FiO 2 = 0.10 - 24 hours) on glutamatergic synaptic transmission and the interaction neuron-astrocyte in neurons of the nucleus tractus solitarius (NTS). Tractus solita...
Article
Obstructive sleep apnea patients face episodes of chronic intermittent hypoxia (CIH), which has been suggested as a causative factor for increased sympathetic activity (SNA) and hypertension. Female rats exposed to CIH develop hypertension and exhibit changes in respiratory-sympathetic coupling, marked by an increase in the inspiratory modulation o...
Article
New findings: What is the central question of this study? After sino-aortic denervation (SAD) rats present normal levels of mean arterial pressure (MAP), high MAP variability and changes in breathing. However, mechanisms involved in SAD-induced respiratory changes and their impact on the modulation of sympathetic activity remain unclear. Herein, w...
Article
Full-text available
At rest, inspiration is an active process while expiration is passive. However, high chemical drive (hypercapnia or hypoxia) activates central and peripheral chemoreceptors triggering reflex increases in inspiration and active expiration. The Locus Coeruleus contains noradrenergic neurons (A6 neurons) that increase their firing frequency when expos...
Article
Full-text available
The carotid bodies are peripheral chemoreceptors and contribute to the homeostatic maintenance of arterial levels of O2, CO2 and [H+]. They have attracted much clinical interest recently because of the realisation that aberrant signalling in these organs is associated with several pathologies including hypertension. Herein, we describe data suggest...
Technical Report
Full-text available
O avanço da ciência, e sua relação com a formação de pessoal altamente qualificado na pós-graduação, geram pressões por desempenho e, em paralelo, dilemas éticos e conflitos de interesse entre os diversos atores envolvidos. A situação urge reflexões sobre quais são tais conflitos e como tratá-los, de forma a que sejam compatíveis com a formação de...
Article
Full-text available
New findings: What is the central question of this study? Chronic intermittent hypoxia (CIH) and one-kidney, one-clip experimental models lead to sympathetic overactivity and hypertension. The present study explored the impact of previous exposure to CIH on one-kidney, one-clip renal hypertension; we hypothesized that CIH potentiates its developme...
Article
Full-text available
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...
Article
Full-text available
Sympathetic activity displays rhythmic oscillations generated by brainstem inspiratory and expiratory neurons. Amplication of these rhythmic respiratory-related oscillations is observed in rats under enhanced central respiratory drive or during the development of neurogenic hypertension. Herein, we evaluated the involvement of ventral medullary sym...
Article
Obstructive sleep apnea (OSA) is a complex disease in which humans face episodes of intermittent hypoxia and it affects men and women. Patients with OSA present hypertension and sympathetic overactivity among several other dysfunctions. Therefore, one important question remains: are the autonomic dysfunctions associated with OSA similar in male and...
Article
The activity of pre-sympathetic neurons is under respiratory modulation and changes in the central respiratory network may impact on the baseline sympathetic activity and mean arterial pressure (MAP). It is well known that after baroreceptor afferents removal (sino-aortic denervation, SAD), rats present an unexpected normal levels of MAP. We hypoth...
Article
Full-text available
In spite of recent advances on the knowledgement of the neural control of cardiovascular function, the cause of sympathetic overactivity in neurogenic hypertension remains unknown. Studies from our laboratory point out that rats submitted to chronic intermittent hypoxia (CIH), an experimental model of neurogenic hypertension, present changes in the...
Article
After recent very successful IUPS Congresses in San Diego (U.S., 2005), Kyoto (Japan, 2009), and Birmingham (UK, 2013), now it is the time for a new journey for the physiologists to stop in Rio de Janeiro (Brazil, 2017). The World Congress of the International Union of Physiological Sciences (IUPS)
Conference Paper
Full-text available
Humans ascending to high altitudes are submitted to sustained hypoxia (SH), activating peripheral chemoreflex with several autonomic and respiratory responses. We analyzed the effect of short-term SH (24 hours, FIO210%) on the cardiovascular parameters in non-anesthetized rats and on the processing of cardiovascular and respiratory reflexes using i...
Article
Full-text available
Although it is well known that chronic hypoxia induces muscle wasting, the effects of intermit-tent hypoxia on skeletal muscle protein metabolism remains unclear. We hypothesized that acute intermittent hypoxia (AIH), a challenge that activates the hypothalamic-pituitary-adrenal axis, would alter muscle protein homeostasis through a glucocorticoid-...
Article
Full-text available
Despite several studies describing the electrophysiological properties of RVLM presympathetic neurons, there is no consensus in the literature about their pacemaking property, mainly due to different experimental approaches used for recordings of neuronal intrinsic properties. In this review we are presenting a historical retrospective about the pi...
Article
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In view of the high proportion of individuals with resistance to antihypertensive medication and/or poor compliance or tolerance of this medication, new drugs to treat hypertension are urgently needed. Here we show that peripheral chemoreceptors generate aberrant signaling that contributes to high blood pressure in hypertension. We discovered that...
Article
Sino-aortic denervated (SAD) rats present mean arterial pressure (MAP) similar to control rats. Since respiration modulates MAP, we hypothesized that conscious SAD rats present respiratory changes associated with the normal MAP. In this study we evaluated the cardiovascular and respiratory activities and arterial blood gases in control and SAD rats...
Article
Chronic intermittent hypoxia (CIH) induces sympathetic overactivity and hypertension in male rats. Enhanced respiratory modulation of sympathetic activity in juvenile male rats exposed to CIH occurs in the expiratory phase of the respiratory cycle, characterizing changes in respiratory-sympathetic coupling. Different from other experimental models...
Article
Full-text available
Chronic intermittent hypoxia (CIH) produces respiratory-related sympathetic overactivity and hypertension in rats. In this study, we tested the hypothesis that the enhanced central respiratory modulation of sympathetic activity after CIH also decreases the sympathoinhibitory component of baroreflex of rats, which may contribute to the development o...
Article
Obstructive Sleep Apnea (OSA) is known to be independently associated with several cardiovascular diseases including hypertension, myocardial infarction and stroke. To determine how OSA can increase cardiovascular risk, animal models have been developed to explore the underlying mechanisms and the cellular and end-organ targets of the predominant p...
Article
Full-text available
Rats exposed to chronic intermittent hypoxia (CIH) develop hypertension, which is associated with changes in the coupling of sympathetic and respiratory activities. In this study we hypothesized that previous preconditioning to intermittent or sustained hypoxia would affect cardiovascular and respiratory changes produced by subsequent protocols of...
Article
Full-text available
Humans ascending to high altitudes are submitted to sustained hypoxia (SH), activating peripheral chemoreflex with several autonomic and respiratory responses. Here we analyzed the effect of short-term SH (24 h, FIO210%) on the processing of cardiovascular and respiratory reflexes using an in situ preparation of rats. SH increased both the sympatho...
Article
Full-text available
Why sympathetic activity raises in neurogenic hypertension remains unknown. It has been postulated that changes in the electrical excitability of medullary pre-sympathetic neurones are the main causal mechanism for the development of sympathetic over activity in experimental hypertension. Herein, we review recent data suggesting that enhanced sympa...
Article
Full-text available
New findings: What is the central question of this study? Chronic intermittent hypoxia (CIH) induces hypertension in male rats. There is evidence that the development of high blood pressure in females is attenuated in other models of hypertension. Due to the lack of information about the cardiovascular effect of CIH in female rats, we set out to d...
Article
Full-text available
Key points: The respiratory control of the glottis by laryngeal motoneurones is characterized by inspiratory abduction and post-inspiratory adduction causing decreases and increases in upper airway resistance, respectively. Chronic intermittent hypoxia (CIH), an important component of obstructive sleep apnoea, exaggerated glottal abduction (before...
Article
Abstract Respiratory modulation seen in the sympathetic nerve activity (SNA) implies that the respiratory and sympathetic networks interact. During hypertension elicited by chronic intermittent hypoxia (CIH), the SNA displays an enhanced respiratory modulation reflecting strengthened interactions between the networks. In this chapter, we review a s...
Article
The respiratory modulation of sympathetic activity relies on the balance between excitatory and inhibitory inputs from the brainstem respiratory network to presympathetic neurons of the rostral ventrolateral medulla. This central respiratory-sympathetic contributes for the generation of respiratory-related rhythmical oscillations in heart rate and...
Article
Full-text available
Major evolutionary trends in animal physiology have been heavily influenced by atmospheric O 2 levels. Amongst other important factors, the increase in atmospheric O 2 which occurred in the Pre-Cambrian and the development of aerobic respiration beckoned the evolution of animal organ systems that were dedicated to the absorption and transportation...
Article
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Introduction The central nucleus of amygdala plays an important role mediating fear and anxiety responses. It is known that oxytocin microinjections into the central nucleus of amygdala induce hypergrooming, an experimental model of compulsive behavior. We evaluated the behavioral and cardiorespiratory responses of conscious rats microinjected with...
Article
The pre-sympathetic neurons in the rostral ventrolateral medulla (RVLM) are considered the source of the sympathetic activity and there is experimental evidence that these cells present intrinsic auto-depolarization. There is also evidence that an important respiratory neuronal population located in the RVLM/Bötzinger complex (BötC) corresponds to...
Article
Full-text available
A major aspect of hypertension is excessive sympathetic activity but the reasons for this remain elusive. Sympathetic tone is increased in the spontaneously hypertensive (SH) rat reflecting, in part, enhanced respiratory-sympathetic coupling. We aimed to identify which respiratory cells might have altered properties. Using the working heart-brain s...
Article
Full-text available
Individuals experiencing sustained hypoxia (SH) exhibit adjustments in the respiratory and autonomic functions by neural mechanisms not yet elucidated. In the present study we evaluated the central mechanisms underpinning the SH-induced changes in the respiratory pattern and their impact on the sympathetic outflow. Using a decerebrated arterially-p...
Article
Full-text available
The respiratory pattern generator modulates the sympathetic outflow, the strength of which is enhanced by challenges produced by hypoxia. This coupling is due to the respiratory-modulated presympathetic neurons in the rostral ventrolateral medulla (RVLM), but the underlining electrophysiological mechanisms remain unclear. For a better understanding...
Article
Full-text available
There is evidence that sympathoexcitatory and respiratory responses to chemoreflex activation involve ventrolateral medulla-projecting nucleus tractus solitarius (NTS) neurons (NTS-VLM neurons) and also that ATP modulates this neurotransmission. Here, we evaluated whether or not astrocytes is the source of endogenous ATP modulating the synaptic tra...
Article
We hypothesize that a local adenosine-5'-triphosphate (ATP) - nitric oxide (NO) - N-methyl-D-aspartate (NMDA) glutamate receptor interaction in the PVN modulates the baseline mean arterial pressure (MAP) and heart rate (HR) in unanesthetized rats. The microinjection of α, β - Methylene ATP (Methyl ATP, 0.06, 0.12, 1.2 nmol/100nL) into the PVN cause...
Conference Paper
Short-term sustained hypoxia (SH, 24 hrs) produces changes in the respiratory motor activity. However, the neurochemical and electrophysiological basis of these changes are poorly understood. In the present study, we evaluated the central mechanisms underlying the respiratory changes induced by SH (10% O2) and the correlated changes in sympathetic...
Article
Second order neurons in the nucleus tractus solitarius (NTS) process and integrate the afferent information from arterial baroreceptors with high fidelity and precise timing synaptic transmission. Since 2nd-order NTS neurons receiving baroreceptors inputs are relatively well characterized, their electrophysiological profile has been accepted as a g...
Article
Full-text available
Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autono...
Article
Full-text available
Why should researchers in charge of basic and clinical investigation of hypertension also pay attention to respiration? More than its primary role to orchestrate the diaphragm, chest, and abdominal muscle contraction and relaxation, essential for O(2) and CO(2) pulmonary exchanges, the brain stem respiratory network is also precise and timely conne...