27 results on '"Accorsi-Mendonça D"'
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2. The balloon catheter induces an increase in contralateral carotid artery reactivity to angiotensin II and phenylephrine
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Accorsi-Mendonça, D, Corrêa, F M A, Paiva, T B, de Souza, H P, Laurindo, F R M, and de Oliveira, A M
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Male ,Time Factors ,Dose-Response Relationship, Drug ,Carotid Artery, Common ,Angiotensin II ,In Vitro Techniques ,Catheterization ,Membrane Potentials ,Rats ,Phenylephrine ,Carotid Arteries ,Commentaries ,Papers ,cardiovascular system ,Humans ,Animals ,Vascular Diseases ,Rats, Wistar ,Carotid Artery Injuries ,Angioplasty, Balloon - Abstract
1. The effects of balloon injury on the reactivity of ipsilateral and contralateral carotid arteries were compared to those observed in arteries from intact animals (control arteries). 2. Carotid arteries were obtained from Wistar rats 2, 4, 7, 15, 30 or 45 days after injury and mounted in an isolated organ bath. Reactivity to angiotensin II (Ang II), phenylephrine (Phe) and bradykinin (BK) was studied. Curves were constructed in the absence or presence of endothelium or after incubation with 10 microm indomethacin, 500 microm valeryl salicylate or 0.1 microm celecoxib. 3. Phe, Ang II and BK maximum effects (Emax) were decreased in ipsilateral arteries when compared to control arteries. No differences were observed among pD2 or Hill coefficient. 4. Emax to Phe (4 and 7 days) and to Ang II (15 and 30 days) increased in the contralateral artery. In addition, Phe or Ang II reactivity was not significantly different in aorta rings from control or carotid-injured animals. 5. The increased responsiveness of contralateral artery was not due to changes in carotid blood flow or resting membrane potential. The endothelium-dependent inhibitory component is not present in the contraction of contralateral arteries and it is not related to superoxide anion production. 6. Indomethacin decreased contralateral artery responsiveness to Phe and Ang II. Valeryl salicylate reduced the Ang II response in contralateral and control arteries. Celecoxib decreased the Phe Emax of contralateral artery. 7. In conclusion, decreased endothelium-derived factors and increased prostanoids appear to be responsible for the increased reactivity of contralateral arteries after injury.
- Published
- 2004
3. Synaptic profile of nucleus tractus solitarius neurons involved with the peripheral chemoreflex pathways
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Accorsi-Mendonça, D., primary, Castania, J.A., additional, Bonagamba, L.G.H., additional, Machado, B.H., additional, and Leão, R.M., additional
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- 2011
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4. Synaptic properties of peripheral chemoreflex second-order neurons in the NTS of rats
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Accorsi-Mendonça, D., primary, Castania, J.A., additional, Bonagamba, L.G.H., additional, Machado, B.H., additional, and Leão, R.X., additional
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- 2011
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5. P7.3 Different approaches to evaluate an interaction of purinergic and nitrergic mechanisms in the nucleus tractus solitarius neurons of rats
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Granjeiro, E.M., primary, Pajolla, G.P., additional, Accorsi-Mendonça, D., additional, Bonagamba, L.G.H., additional, Leão, R.M., additional, and Machado, B.H., additional
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- 2009
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6. Influence of Estrogen and/or Progesterone on Isolated Ovariectomized Rat Uterus
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Accorsi-Mendonça, D., primary, Corrêa, F.M.A., additional, Anselmo-Franci, J.A., additional, and de Oliveira, A.M., additional
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- 2002
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7. Angiotensin Actions on the Isolated Rat Uterus during the Estrous Cycle: Influence of Resting Membrane Potential and Uterine Morphology
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Accorsi-Mendonça, D., primary, Corrêa, F.M.A., additional, Anselmo-Franci, J.A., additional, Paiva, T.B., additional, and de Oliveira, A.M., additional
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- 2002
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8. Sustained hypoxia increases excitatory transmission in the nucleus tractus solitarius neurons of juvenile rats.
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Accorsi-Mendonça, D., Almado, C. L., and Machado, B. H.
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NEURAL transmission , *SOLITARY nucleus , *NEURONS - Abstract
In previous studies we verified that the synaptic transmission in the nucleus tractus solitarius (NTS) neurons is affected by chronic intermittent hypoxia. Here we evaluated the effect of short-term sustained hypoxia (SH, 24 hours - 10% O2) on the intrinsic properties and synaptic transmission of NTS neurons in the brainstem slices from young rats (3 weeks old) using whole cell patch clamp technique. SH produced no change in resting membrane potential [control: -78.7 ± 2.4 mV (n=15), SH: -72.3 ± 3.7 mV, (n=15)], input resistance [control: 1.4 ± 0.4 GOhm (n=8), SH: 1.4 ± 0.4 GOhm, (n=9)] and capacitance of NTS neurons [control: 14.2 ± 0.9 pF (n=17), SH: 12.4 ± 0.8 pF (n=15)]. However, SH increased the frequency of spontaneous excitatory post-synaptic currents [(sEPSCs) control: 3.6 ± 0.4 Hz (n=18), SH: 7 ± 1.5 pF, (n=15), p<0.05] and the amplitude of evoked excitatory post-synaptic currents [(eEPSCs) control: -289 ± 51 pA (n=15), SH: -472 ± 64 pA (n=15), p<0.05]. Moreover, SH also increased the depression of evoked excitatory post-synaptic currents after five stimuli on afferent fibers in the tractus solitarius [amplitude of 5 evoked currents of control group: 100%, 44%, 34%, 32% and 28% (n=15), amplitude of 5 evoked currents of SH group: 100%, 40%, 28%, 22% and 17% (n=15) *p<0,001 - Two way ANOVA]. These findings suggest that SH affect the excitatory transmission in NTS neurons increasing the release probability in the pre-synaptic terminal. We conclude that 24 hours of SH enhances spontaneous and evoked excitatory synaptic transmission on NTS neurons but does not change their intrinsic properties. These alterations in the synaptic transmission in the NTS neurons induced by SH may play a critical role in the cardiovascular and respiratory problems observed in high altitude. [ABSTRACT FROM AUTHOR]
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- 2013
9. Enhancement of the Evoked Excitatory Transmission in the Nucleus Tractus Solitarius Neurons after Sustained Hypoxia in Mice Depends on A 2A Receptors.
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Souza JR, Lima-Silveira L, Accorsi-Mendonça D, and Machado BH
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- Rats, Mice, Animals, Synaptic Transmission physiology, Hypoxia, Adenosine, Solitary Nucleus physiology, Neurons physiology
- Abstract
The first synapses of the afferents of peripheral chemoreceptors are located in the Nucleus Tractus Solitarius (NTS) and there is evidence that short-term sustained hypoxia (SH - 24 h, FiO
2 0.1) facilitates glutamatergic transmission in NTS neurons of rats. Adenosine is an important neuromodulator of synaptic transmission and hypoxia contributes to increase its extracellular concentration. The A2A receptors mediate the excitatory actions of adenosine and are active players in the modulation of neuronal networks in the NTS. Herein, we used knockout mice for A2A receptors (A2A KO) and electrophysiological recordings of NTS neurons were performed to evaluate the contribution of these receptors in the changes in synaptic transmission in NTS neurons of mice submitted to SH. The membrane passive properties and excitability of NTS neurons were not affected by SH and were similar between A2A KO and wild-type mice. The overall amplitude of spontaneous glutamatergic currents in NTS neurons of A2A KO mice was lower than in Balb/c WT mice. SH increased the amplitude of evoked glutamatergic currents of NTS neurons from WT mice by a non-presynaptic mechanism, but this enhancement was not observed in NTS neurons of A2A KO mice. Under normoxia, the amplitude of evoked glutamatergic currents was similar between WT and A2A KO mice. The data indicate that A2A receptors (a) modulate spontaneous glutamatergic currents, (b) do not modulate the evoked glutamatergic transmission in the NTS neurons under control conditions, and (c) are required for the enhancement of glutamatergic transmission observed in the NTS neurons of mice submitted to SH., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)- Published
- 2024
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10. Retraction notice to: "Sustained Hypoxia Reduces GABAergic Modulation on NTS Neurons Sending Projections to Ventral Medulla of Rats" [Neuroscience 457 (2021) 1-11.
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Pascoaloti-Lima JC, Machado BH, and Accorsi-Mendonça D
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- 2022
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11. Sustained Hypoxia Reduces GABAergic Modulation on NTS Neurons Sending Projections to Ventral Medulla of Rats.
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Pascoaloti-Lima JC, Machado BH, and Accorsi-Mendonça D
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- Animals, Hypoxia, Neurons, Rats, Rats, Wistar, Synaptic Transmission, Medulla Oblongata, Solitary Nucleus
- Abstract
Peripheral chemoreflex is activated during short-term sustained hypoxia (SH), and the first synapse of these afferents is located in Nucleus Tractus Solitarius(NTS). NTS neurons projecting to the ventral lateral medulla (NTS-VLM) are part of the respiratory pathways of the chemoreflex. SH increases the magnitude of basal respiratory parameters in rats from Wistar-Hannover strain. In this study, we hypothesized that the observed changes in the respiratory pattern in response to SH were due to changes in the GABAergic modulation of the synaptic transmission of NTS-VLM neurons. We used an electrophysiological approach to record the synaptic activity of NTS neurons labeled with a retrograde tracer previously microinjected into VLM of Wistar-Hannover rats submitted to 24 h SH. The data are showing that: (a) the amplitude of evoked inhibitory currents in NTS-VLM neurons of SH rats was reduced and not accompanied by any change in rise-time and decay-time; (b) the 1/CV
2 and the number of failures in response to evoked currents were also affected by SH; (c) the frequency of spontaneous inhibitory currents was reduced by SH without changes in amplitude and half-width. These effects of SH were observed in NTS-VLM neurons located in caudal and intermediate NTS, but not in NTS-VLM neurons located in the rostral NTS. We conclude that SH causes a reduction in inhibitory modulation onto NTS-VLM neurons by pre-synaptic mechanisms, which may contribute to the observed changes in the respiratory pattern of Wistar-Hannover rats submitted to SH., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)- Published
- 2021
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12. Enhancement of excitatory transmission in NTS neurons projecting to ventral medulla of rats exposed to sustained hypoxia is blunted by minocycline.
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Lima-Silveira L, Accorsi-Mendonça D, Bonagamba LGH, Almado CEL, da Silva MP, Nedoboy PE, Pilowsky PM, and Machado BH
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- Animals, Arterial Pressure drug effects, Excitatory Postsynaptic Potentials, Male, Microglia physiology, Neurons physiology, Rats, Wistar, Solitary Nucleus physiology, Hypoxia physiopathology, Minocycline pharmacology, Neurons drug effects, Solitary Nucleus drug effects
- Abstract
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 the amplitude of glutamatergic postsynaptic currents in the NTS-VLM neurons, induced by postsynaptic mechanisms, was blunted by minocycline treatment. The number of microglial cells was increased in the NTS of vehicle-treated SH rats but not in the NTS of minocycline-treated rats. The data show that microglial recruitment/proliferation induced by SH is associated with the enhancement of excitatory neurotransmission in NTS-VLM neurons, which may contribute to the observed increase in AP., Abstract: Short-term sustained hypoxia (SH) produces significant autonomic and respiratory adjustments and triggers activation of microglia, the resident immune cells in the brain. SH also enhances glutamatergic neurotransmission in the NTS. Here we evaluated the role of microglial activation induced by SH on the cardiovascular changes and mainly on glutamatergic neurotransmission in NTS neurons sending projections to the ventrolateral medulla (NTS-VLM), using a microglia inhibitor (minocycline). Direct measurement of arterial pressure (AP) in freely moving rats showed that SH (24 h, fraction of inspired oxygen ( F I , O 2 ) 0.1) in vehicle and minocycline (30 mg/kg i.p. for 3 days)-treated groups produced a significant increase in AP in relation to control groups under normoxic conditions, but this increase was significantly lower in minocycline-treated rats. Whole-cell patch-clamp recordings revealed that the active properties of the membrane were comparable among the groups. Nevertheless, the amplitudes of glutamatergic postsynaptic currents, evoked by tractus solitarius stimulation, were increased in NTS-VLM neurons of SH rats. Changes in asynchronous glutamatergic currents indicated that the observed increase in amplitude was due to postsynaptic mechanisms. These changes were blunted in the SH group previously treated with minocycline. Using immunofluorescence, we found that the number of microglial cells was increased in the NTS of vehicle-treated SH rats but not in the NTS neurons of minocycline-treated rats. Our data support the concept that microglial activation induced by SH is associated with the enhancement of excitatory neurotransmission in NTS-VLM neurons, which may contribute to the increase in AP observed in this experimental model., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)
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- 2019
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13. Astrocytic modulation of glutamatergic synaptic transmission is reduced in NTS of rats submitted to short-term sustained hypoxia.
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Accorsi-Mendonça D, Bonagamba LGH, and Machado BH
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- Animals, Astrocytes drug effects, Astrocytes physiology, Excitatory Amino Acid Agonists pharmacology, Excitatory Amino Acid Antagonists pharmacology, Fluoroacetates pharmacology, Hypoxia metabolism, Kainic Acid pharmacology, Male, Membrane Potentials, Neurons drug effects, Neurons physiology, Rats, Rats, Wistar, Solitary Nucleus metabolism, Astrocytes metabolism, Glutamic Acid pharmacology, Hypoxia physiopathology, Solitary Nucleus physiopathology, Synaptic Transmission
- Abstract
Sustained hypoxia (SH) activates chemoreceptors to produce cardiovascular and respiratory responses to bring the arterial partial pressure of O
2 back to the physiological range. We evaluated the effect of SH (fraction of inspired O2 = 0.10, 24 h) on glutamatergic synaptic transmission and the interaction neuron-astrocyte in neurons of the nucleus tractus solitarii (NTS). Tractus solitarius (TS) fiber stimulation induced glutamatergic currents in neurons and astrocytes. SH increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/kainate) [-183 ± 122 pA ( n = 10) vs. -353 ± 101 pA ( n = 10)] and N -methyl-d-aspartate (NMDA) current amplitude [61 ± 10 pA ( n = 7) vs. 102 ± 37 pA ( n = 10)]. To investigate the effects of SH, we used fluoroacetate (FAC), an astrocytic inhibitor, which revealed an excitatory modulation on AMPA/kainate current and an inhibitory modulation of NMDA current in control rats. SH blunted the astrocytic modulation of AMPA [artificial cerebrospinal fluid (aCSF): -353 ± 101 pA vs. aCSF + FAC: -369 ± 76 pA ( n = 10)] and NMDA currents [aCSF: 102 ± 37 pA vs. aCSF + FAC: 108 ± 32 pA ( n = 10)]. SH increased AMPA current density [control: -6 ± 3.5 pA/pF ( n = 6) vs. SH: -20 ± 12 pA/pF ( n = 7)], suggesting changes in density, conductance, or affinity of AMPA receptors. SH produced no effect on astrocytic resting membrane potential, input resistance, and AMPA/kainate current. We conclude that SH decreased the neuron-astrocyte interaction at the NTS level, facilitating the glutamatergic transmission, which may contribute to the enhancement of cardiovascular and respiratory responses to baro- and chemoreflexes activation in SH rats. NEW & NOTEWORTHY Using an electrophysiological approach, we have shown that in nucleus tractus solitarii (NTS) from control rats, astrocytes modulate the AMPA and NMDA currents in NTS neurons, changing their excitability. Sustained hypoxia (SH) increased both glutamatergic currents in NTS neurons due to 1 ) a reduction in the astrocytic modulation and 2 ) an increase in the density of AMPA receptors. These new findings show the importance of neuron-astrocyte modulation in the excitatory synaptic transmission in NTS of control and SH rats.- Published
- 2019
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14. Corrigendum: Pacemaking Property of RVLM Presympathetic Neurons.
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Accorsi-Mendonça D, da Silva MP, Souza GM, Lima-Silveira L, Karlen-Amarante M, Amorim MR, Almado CE, Moraes DJ, and Machado BH
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[This corrects the article on p. 424 in vol. 7, PMID: 27713705.].
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- 2016
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15. Pacemaking Property of RVLM Presympathetic Neurons.
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Accorsi-Mendonça D, da Silva MP, Souza GM, Lima-Silveira L, Karlen-Amarante M, Amorim MR, Almado CE, Moraes DJ, and Machado BH
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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 pioneering studies and their controversies on the intrinsic electrophysiological property of auto-depolarization of these cells in conjunction with recent studies from our laboratory documenting that RVLM presympathetic neurons present pacemaking capacity. We also discuss whether increased sympathetic activity observed in animal models of neurogenic hypertension (CIH and SHR) are dependent on changes in the intrinsic electrophysiological properties of these cells or due to changes in modulatory inputs from neurons of the respiratory network. We also highlight the key role of I
NaP as the major current contributing to the pacemaking property of RVLM presympathetic neurons.- Published
- 2016
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16. Enhanced Firing in NTS Induced by Short-Term Sustained Hypoxia Is Modulated by Glia-Neuron Interaction.
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Accorsi-Mendonça D, Almado CE, Bonagamba LG, Castania JA, Moraes DJ, and Machado BH
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- 4-Aminopyridine pharmacology, Afferent Pathways physiology, Amino Acids, Animals, Baroreflex drug effects, Bicuculline pharmacology, GABA-A Receptor Antagonists pharmacology, Heart Rate physiology, In Vitro Techniques, Male, Potassium Channel Blockers pharmacology, Pressoreceptors drug effects, Rats, Rats, Wistar, Sympathetic Nervous System physiopathology, Action Potentials physiology, Chemoreceptor Cells physiology, Hypoxia pathology, Neuroglia physiology, Solitary Nucleus pathology
- Abstract
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-inhibitory and bradycardiac components of baroreflex and the sympathetic and respiratory responses of peripheral chemoreflex. Electrophysiological properties and synaptic transmission in the nucleus tractus solitarius (NTS) neurons, the first synaptic station of afferents of baroreflexes and chemoreflexes, were evaluated using brainstem slices and whole-cell patch-clamp. The second-order NTS neurons were identified by previous application of fluorescent tracer onto carotid body for chemoreceptor afferents or onto aortic depressor nerve for baroreceptor afferents. SH increased the intrinsic excitability of NTS neurons. Delayed excitation, caused by A-type potassium current (IKA), was observed in most of NTS neurons from control rats. The IKA amplitude was higher in identified second-order NTS neurons from control than in SH rats. SH also blunted the astrocytic inhibition of IKA in NTS neurons and increased the synaptic transmission in response to afferent fibers stimulation. The frequency of spontaneous excitatory currents was also increased in neurons from SH rats, indicating that SH increased the neurotransmission by presynaptic mechanisms. Therefore, short-term SH changed the glia-neuron interaction, increasing the excitability and excitatory transmission of NTS neurons, which may contribute to the observed increase in the reflex sensitivity of baroreflex and chemoreflex in in situ preparation., (Copyright © 2015 the authors 0270-6474/15/356903-15$15.00/0.)
- Published
- 2015
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17. Evolution and physiology of neural oxygen sensing.
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Costa KM, Accorsi-Mendonça D, Moraes DJ, and Machado BH
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Major evolutionary trends in animal physiology have been heavily influenced by atmospheric O2 levels. Amongst other important factors, the increase in atmospheric O2 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 of O2, e.g., the respiratory and cardiovascular systems of vertebrates. Global variations of O2 levels in post-Cambrian periods have also been correlated with evolutionary changes in animal physiology, especially cardiorespiratory function. Oxygen transportation systems are, in our view, ultimately controlled by the brain related mechanisms, which senses changes in O2 availability and regulates autonomic and respiratory responses that ensure the survival of the organism in the face of hypoxic challenges. In vertebrates, the major sensorial system for oxygen sensing and responding to hypoxia is the peripheral chemoreflex neuronal pathways, which includes the oxygen chemosensitive glomus cells and several brainstem regions involved in the autonomic regulation of the cardiovascular system and respiratory control. In this review we discuss the concept that regulating O2 homeostasis was one of the primordial roles of the nervous system. We also review the physiology of the peripheral chemoreflex, focusing on the integrative repercussions of chemoreflex activation and the evolutionary importance of this system, which is essential for the survival of complex organisms such as vertebrates. The contribution of hypoxia and peripheral chemoreflex for the development of diseases associated to the cardiovascular and respiratory systems is also discussed in an evolutionary context.
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- 2014
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18. Glial cells modulate the synaptic transmission of NTS neurons sending projections to ventral medulla of Wistar rats.
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Accorsi-Mendonça D, Zoccal DB, Bonagamba LG, and Machado BH
- Abstract
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 transmission in NTS-VLM neurons. Synaptic activities of putative astrocytes or NTS-VLM neurons were recorded using whole cell patch clamp. Tractus solitarius (TS) stimulation induced TS-evoked excitatory postsynaptic currents (TS-eEPSCs) in NTS-VLM neurons as well in NTS putative astrocytes, which were also identified by previous labeling. Fluoracetate (FAC), an inhibitor of glial metabolism, reduced TS-eEPSCs amplitude (-85.6 ± 16 vs. -39 ± 7.1 pA, n = 12) and sEPSCs frequency (2.8 ± 0.5 vs. 1.8 ± 0.46 Hz, n = 10) in recorded NTS-VLM neurons, indicating a gliomodulation of glutamatergic currents. To verify the involvement of endogenous ATP a purinergic antagonist was used, which reduced the TS-eEPSCs amplitude (-207 ± 50 vs. -149 ± 50 pA, n = 6), the sEPSCs frequency (1.19 ± 0.2 vs. 0.62 ± 0.11 Hz, n = 6), and increased the paired-pulse ratio (PPR) values (∼20%) in NTS-VLM neurons. Simultaneous perfusion of Pyridoxalphosphate-6-azophenyl-2',5'-disulfonic acid (iso-PPADS) and FAC produced reduction in TS-eEPSCs similar to that observed with iso-PPADS or FAC alone, indicating that glial cells are the source of ATP released after TS stimulation. Extracellular ATP measurement showed that FAC reduced evoked and spontaneous ATP release. All together these data show that putative astrocytes are the source of endogenous ATP, which via activation of presynaptic P2X receptors, facilitates the evoked glutamate release and increases the synaptic transmission efficacy in the NTS-VLM neurons probably involved with the peripheral chemoreflex pathways.
- Published
- 2013
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19. Synaptic transmission of baro- and chemoreceptors afferents in the NTS second order neurons.
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Accorsi-Mendonça D and Machado BH
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- Animals, Excitatory Postsynaptic Potentials physiology, Humans, Neurons physiology, Chemoreceptor Cells physiology, Pressoreceptors physiology, Solitary Nucleus physiology, Synaptic Transmission physiology
- Abstract
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 general characteristic for all 2nd-order NTS neurons involved with the processing of different sensorial inputs. On the other hand, the synaptic properties of other afferent systems in NTS, such as the peripheral chemoreceptors, are not yet well understood. In this context, in previous studies we demonstrated that in response to repetitive afferents stimulation, the chemoreceptors 2nd-order NTS neurons also presented high fidelity of synaptic transmission, but with a large variability in the latency of evoked responses. This finding is different in relation to the precise timing transmission for baroreceptor 2nd-order NTS neurons, which was accepted as a general characteristic profile for all 2nd order neurons in the NTS. In this brief review we discuss this new concept as an index of complexity of the sensorial inputs to NTS with focus on the synaptic processing of baro- and chemoreceptor afferents., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2013
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20. Interaction of purinergic and nitrergic mechanisms in the caudal nucleus tractus solitarii of rats.
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Granjeiro EM, Pajolla GP, Accorsi-Mendonça D, and Machado BH
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- Adenosine Triphosphate metabolism, Adenosine Triphosphate pharmacology, Animals, Arginine analogs & derivatives, Arginine pharmacology, Blood Pressure drug effects, Blood Pressure physiology, Brain Stem anatomy & histology, Brain Stem drug effects, Cardiovascular Physiological Phenomena drug effects, Enzyme Inhibitors pharmacology, Fluorescein, Fluorescent Dyes, Male, Microinjections, Nitrergic Neurons drug effects, Nitrergic Neurons metabolism, Nitric Oxide Synthase Type I antagonists & inhibitors, Nitric Oxide Synthase Type I metabolism, Organ Culture Techniques, Rats, Rats, Wistar, Respiratory Physiological Phenomena drug effects, Respiratory Rate drug effects, Respiratory Rate physiology, Solitary Nucleus anatomy & histology, Solitary Nucleus drug effects, Staining and Labeling, Brain Stem metabolism, Nitric Oxide metabolism, Purines metabolism, Solitary Nucleus metabolism
- Abstract
The interaction of purinergic and nitrergic mechanisms was evaluated in the caudal nucleus tractus solitarii (cNTS) using awake animals and brainstem slices. In awake animals, ATP (1.25 nmol/50 nL) was microinjected into the cNTS before and after the microinjection of a selective neuronal nitric oxide synthase (nNOS) inhibitor N-propyl-l-arginine (NPLA, 3 pmoles/50 nL, n=8) or vehicle (saline, n=4), and cardiovascular and ventilatory parameters were recorded. In brainstem slices from a distinct group of rats, the effects of ATP on the NO concentration in the cNTS using the fluorescent dye DAF-2 DA were evaluated. For this purpose brainstem slices (150 microm) containing the cNTS were pre-incubated with ATP (500 microM; n=8) before and during DAF-2 DA loading. Microinjection of ATP into the cNTS increases the arterial pressure (AP), respiratory frequency (f(R)) and minute ventilation (V(E)), which were significantly reduced by pretreatment with N-PLA, a selective nNOS inhibitor (AP: 39+/-3 vs 16+/-14 mm Hg; f(R): 75+/-14 vs 4+/-3 cpm; V(E): 909+/-159 vs 77+/-39 mL kg(-1) m(-1)). The effects of ATP in the cNTS were not affected by microinjection of saline. ATP significantly increased the NO fluorescence in the cNTS (62+/-7 vs 101+/-10 AU). The data show that in the cNTS: a) the NO production is increased by ATP; b) NO formation by nNOS is involved in the cardiovascular and ventilatory responses to microinjection of ATP. Taken together, these data suggest an interaction of purinergic and nitrergic mechanisms in the cNTS.
- Published
- 2009
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21. Immunoreactivity for neuronal NOS and fluorescent indication of NO formation in the NTS of juvenile rats submitted to chronic intermittent hypoxia.
- Author
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Pajolla GP, Accorsi-Mendonça D, Lunardi CN, Bendhack LM, Machado BH, and Llewellyn-Smith IJ
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- Animals, Blood Pressure drug effects, Blood Pressure physiology, Disease Models, Animal, Fluorescein metabolism, Gene Expression Regulation physiology, Heart Rate drug effects, Heart Rate physiology, Indicators and Reagents metabolism, Male, Microscopy, Confocal methods, Rats, Rats, Wistar, Hypoxia pathology, Neurons enzymology, Nitric Oxide metabolism, Nitric Oxide Synthase Type I metabolism, Solitary Nucleus enzymology, Solitary Nucleus pathology
- Abstract
Exposure to chronic intermittent hypoxia (CIH) leads to significant autonomic and respiratory changes, similar to those observed in obstructive sleep apnea. The hypertension associated with CIH is due to sympathoexcitation triggered by long-term exposure to intermittent hypoxia. However, the mechanisms underlying these effects are unknown. Changes in central regulation of sympathetic activity may underlie CIH-induced hypertension. Since NO appears to be mainly sympathoinhibitory in the nucleus of the solitary tract (NTS), we hypothesized that CIH augments sympathetic activity, in part by reducing neuronal nitric oxide synthase (nNOS) expression and consequently nitric oxide (NO) production in this brain region. To test our hypothesis, juvenile male Wistar rats were exposed to CIH for 8 h/day for 10 days and sections of perfused brainstem were either stained to reveal nNOS-immunoreactivity or loaded with DAF 2-DA to label neurons containing NO. CIH rats showed a significant increase in mean arterial pressure and heart rate compared to controls. However, there was no significant difference in the distribution, staining intensity or numbers of nNOS-immunoreactive neurons in the NTS between experimental and control rats. We also found no significant change in NO content in the DAF 2-DA-loaded sections of NTS from CIH rats. Our data show that NO is not altered in the NTS of juvenile CIH rats, suggesting that nitrergic mechanisms, at least in the NTS, are unlikely to be involved in the sympathetic excitation that generates the hypertension observed after 10 days of CIH.
- Published
- 2009
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22. Fluorescent indication that nitric oxide formation in NTS neurons is modulated by glutamate and GABA.
- Author
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Pajolla GP, Accorsi-Mendonça D, Rodrigues GJ, Bendhack LM, Machado BH, and Lunardi CN
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- Animals, Brain Stem metabolism, Fluorescent Dyes, Microscopy, Fluorescence, Nitric Oxide analysis, Rats, Glutamic Acid metabolism, Neurons metabolism, Nitric Oxide biosynthesis, gamma-Aminobutyric Acid metabolism
- Abstract
Nitric oxide (NO) in NTS plays an important role in regulating autonomic function to the cardiovascular system. Using the fluorescent dye DAF-2 DA, we evaluated the NO concentration in NTS. Brainstem slices of rats were loaded with DAF-2 DA, washed, fixed in paraformaldehyde and examined under fluorescent light. In different experimental groups, NTS slices were pre-incubated with 1 mM l-NAME (a non-selective NOS inhibitor), 1 mM d-NAME (an inactive enantiomere of l-NAME), 1 mM kynurenic acid (a non-selective ionotropic receptors antagonist) or 20 microM bicuculline (a selective GABAA receptors antagonist) before and during DAF-2 DA loading. Images were acquired using a confocal microscope and the intensity of fluorescence was quantified in three antero-posterior NTS regions. In addition, slices previously loaded with DAF-2 DA were incubated with NeuN or GFAP antibody. A semi-quantitative analysis of the fluorescence intensity showed that the basal NO concentration was similar in all antero-posterior aspects of the NTS (rostral intermediate, 15.5 +/- 0.8 AU; caudal intermediate, 13.2 +/- 1.4 AU; caudal commissural, 13.8 +/- 1.4 AU, n = 10). In addition, the inhibition of NOS and the antagonism of glutamatergic receptors decreased the NO fluorescence in the NTS. On the other hand, d-NAME did not affect the NO fluorescence and the antagonism of GABAA receptors increased the NO fluorescence in the NTS. It is important to note that the fluorescence for NO was detected mainly in neurons. These data show that the fluorescence observed after NTS loading with DAF-2 DA is a result of NO present in the NTS and support the concept that NTS neurons have basal NO production which is modulated by l-glutamate and GABA.
- Published
- 2009
- Full Text
- View/download PDF
23. Are L-glutamate and ATP cotransmitters of the peripheral chemoreflex in the rat nucleus tractus solitarius?
- Author
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Accorsi-Mendonça D, Bonagamba LG, Leão RM, and Machado BH
- Subjects
- Animals, Electrophysiological Phenomena physiology, Excitatory Postsynaptic Potentials physiology, Male, Neurons physiology, Patch-Clamp Techniques, Rats, Rats, Wistar, Synaptic Transmission physiology, Adenosine Triphosphate physiology, Chemoreceptor Cells physiology, Glutamic Acid physiology, Neurotransmitter Agents physiology, Peripheral Nervous System physiology, Solitary Nucleus physiology
- Abstract
Peripheral chemoreflex activation in awake rats or in the working heart-brainstem preparation (WHBP) produces sympathoexcitation, bradycardia and an increase in the frequency of phrenic nerve activity. Our focus is the neurotransmission of the sympathoexcitatory component of the chemoreflex within the nucleus of the tractus solitarius (NTS), and recently we verified that the simultaneous antagonism of ionotropic glutamate and purinergic P(2) receptors in the NTS blocked the pressor response and increased thoracic sympathetic activity in awake rats and WHBP, respectively, in response to peripheral chemoreflex activation. These previous data suggested the involvement of ATP and L-glutamate in the NTS in the processing of the sympathoexcitatory component of the chemoreflex by unknown mechanisms. For a better understanding of these mechanisms, here we used a patch-clamp approach in brainstem slices to evaluate the characteristics of the synaptic transmission of NTS neurons sending projections to the ventral medulla, which include the premotor neurons involved in the generation of the sympathetic outflow. The NTS neurons sending projections to the ventral medulla were identified by previous microinjection of the membrane tracer dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), in the ventral medulla and the spontaneous (sEPSCs) and tractus solitarius (TS)-evoked excitatory postsynaptic current (TS-eEPSCs) were recorded using patch clamp. With this approach, we made the following observations on NTS neurons projecting to the ventral medulla: (i) the sEPSCs and TS-eEPSCs of DiI-labelled NTS neurons were completely abolished by 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX), an antagonist of ionotropic non-NMDA glutamatergic receptors, showing that they are mediated by L-glutamate; (ii) application of ATP increased the frequency of appearance of spontaneous glutamatergic currents, reflecting an increased exocytosis of glutamatergic vesicles; and (iii) ATP decreased the peak of TS-evoked glutamatergic currents. We conclude that L-glutamate is the main neurotransmitter of spontaneous and TS-evoked synaptic activities in the NTS neurons projecting to the ventral medulla and that ATP has a dual modulatory role on this excitatory transmission, facilitating the spontaneous glutamatergic transmission and inhibiting the TS-evoked glutamatergic transmission. These data also suggest that ATP is not acting as a cotransmitter with L-glutamate, at least at the level of this subpopulation of NTS neurons studied.
- Published
- 2009
- Full Text
- View/download PDF
24. Inhibition of spontaneous neurotransmission in the nucleus of solitary tract of the rat by the cannabinoid agonist WIN 55212-2 is not via CB1 or CB2 receptors.
- Author
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Accorsi-Mendonça D, Almado CE, Dagostin AL, Machado BH, and Leão RM
- Subjects
- Animals, Cannabinoid Receptor Agonists, Cannabinoid Receptor Antagonists, Cannabinoid Receptor Modulators pharmacology, Glutamic Acid metabolism, Inhibitory Postsynaptic Potentials drug effects, Inhibitory Postsynaptic Potentials physiology, Male, Neural Inhibition physiology, Organ Culture Techniques, Patch-Clamp Techniques, Rats, Rats, Wistar, Receptor, Cannabinoid, CB1 agonists, Receptor, Cannabinoid, CB1 antagonists & inhibitors, Receptor, Cannabinoid, CB1 metabolism, Receptor, Cannabinoid, CB2 agonists, Receptor, Cannabinoid, CB2 antagonists & inhibitors, Receptor, Cannabinoid, CB2 metabolism, Solitary Nucleus metabolism, Synaptic Transmission physiology, Visceral Afferents drug effects, Visceral Afferents metabolism, gamma-Aminobutyric Acid metabolism, Benzoxazines pharmacology, Cannabinoids pharmacology, Morpholines pharmacology, Naphthalenes pharmacology, Neural Inhibition drug effects, Receptors, Cannabinoid metabolism, Solitary Nucleus drug effects, Synaptic Transmission drug effects
- Abstract
Cannabinoids have been shown to modulate central autonomic regulation and baroreflex control of blood pressure. Both CB1 and CB2 cannabinoid receptors have been described in the nucleus tractus solitarius (NTS), which receives direct afferent projections of cardiovascular reflexes. In the present study we evaluated the effects of WIN 55212-2 (WIN), a cannabinoid agonist, on fast neurotransmission in the NTS. We recorded spontaneous post-synaptic currents using the whole-cell configuration in NTS cells in brainstem slices from young rats (25-30 days old). Application of 5 microM WIN inhibited the frequency of both glutamatergic and GABAergic sPSCs, without affecting their amplitudes. Effects of WIN were not blocked by application of the CB1 antagonist AM251, the CB2 antagonist AM630 or the vanniloid receptor TRPV1 antagonist AMG9810, suggesting that the effect of WIN is via a non-CB1 non-CB2 receptor. Neither the CB1/CB2 agonist HU210 nor the CB1 agonist ACPA affected the frequency of sPSCs. We conclude WIN inhibits the neurotransmission in the NTS of young rats via a receptor distinct from CB1 or CB2.
- Published
- 2008
- Full Text
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25. Urethane inhibits the GABAergic neurotransmission in the nucleus of the solitary tract of rat brain stem slices.
- Author
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Accorsi-Mendonça D, Leão RM, Aguiar JF, Varanda WA, and Machado BH
- Subjects
- Anesthetics, Local pharmacology, Animals, Diazepam pharmacology, Excitatory Postsynaptic Potentials drug effects, Hypnotics and Sedatives pharmacology, In Vitro Techniques, Male, Membrane Potentials drug effects, Patch-Clamp Techniques, Quinoxalines pharmacology, Rats, Rats, Wistar, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Tetrodotoxin pharmacology, Anesthetics, Intravenous pharmacology, Brain Stem drug effects, Solitary Nucleus drug effects, Synaptic Transmission drug effects, Urethane pharmacology, gamma-Aminobutyric Acid physiology
- Abstract
Because urethane is a widely used anesthetic in animal experimentation, in the present study, we evaluated its effects on neurons of the nucleus of the solitary tract (NTS) in brain stem slices from young rats (25-30 days old). Using the whole cell configuration of the patch-clamp technique, spontaneous postsynaptic currents (sPSCs) and evoked excitatory postsynaptic currents (eEPSCs) were recorded. Urethane (20 mM) decreased by approximately 60% the frequency of GABAergic sPSCs (1.0 +/- 0.2 vs. 0.4 +/- 0.1 Hz) but did not change the frequency, amplitude, or half-width of glutamatergic events or TTX-resistant inhibitory sPSCs [miniature inhibitory postsynaptic currents (IPSCs)]. Miniature IPSCs were measured in the presence of urethane plus 1 mM diazepam (1 mM), and no changes were seen in their amplitude. This suggests that the GABA concentration in the NTS synapses is set at saturating level. We also evaluated the effect of urethane on eEPSCs, and no significant change was observed in the amplitude of N-methyl-d-aspartate [NMDA; 44.2 +/- 11.5 vs. 37.6 +/- 10.6 pA (holding potential = 40 mV)] and non-NMDA currents [204.4 +/- 35.5 vs. 196.6 +/- 31.2 pA (holding potential = -70 mV)]. Current-clamp experiments showed that urethane did not alter the action potential characteristics and passive membrane properties. These data suggest that urethane has an inhibitory effect on GABAergic neurons in the NTS but does not change the spontaneous or evoked excitatory responses.
- Published
- 2007
- Full Text
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26. B(2)-receptor modulation of the reactivity to phenylephrine and angiotensin II in the carotid artery of normotensive rats after trandolapril treatment.
- Author
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Accorsi-Mendonça D, Corrêa FM, and Oliveira AM
- Subjects
- Animals, Bradykinin analogs & derivatives, Bradykinin pharmacology, Carotid Arteries physiology, Endothelium physiology, In Vitro Techniques, Indomethacin pharmacology, Male, Muscle Contraction, NG-Nitroarginine Methyl Ester pharmacology, Peptidyl-Dipeptidase A metabolism, Rats, Rats, Wistar, Angiotensin II pharmacology, Angiotensin-Converting Enzyme Inhibitors pharmacology, Carotid Arteries drug effects, Indoles pharmacology, Phenylephrine pharmacology, Receptors, Adrenergic, beta-2 drug effects
- Abstract
This study was designed to study the effects of angiotensin converting enzyme inhibitors (ACEI) following treatment with trandolapril (0.3 mg kg(-1) day(-1)) on carotid arterial responsiveness in normotensive Wistar rats. Carotid arteries were obtained from control or trandolapril-treated animals and mounted in an isolated organ bath. Reactivity to angiotensin II (Ang II), phenylephrine (Phe) and KCl was studied. Agonist concentration-response curves were constructed in either the absence or presence of the endothelium or after incubation with L-NAME (10(-6) M), HOE140 (10(-7) M) or indomethacin (10(-5) M). Trandolapril treatment decreased the Ang II and Phe potencies in carotid arteries, but did not affect the maximal response. The KCl responses (potency and Emax) were similar in both control and trandolapril-treated arteries. The absence of endothelium increased the response to both agonists in control and trandolapril-treated arteries; however, the inhibitory component from the endothelial layer of the Phe response was greater in trandolapril-treated animals than in control animals. The presence of L-NAME or HOE140 abolished the changes in the potency values of trandolapril-treated animals. The presence of indomethacin did not change the effect of trandolapril on the potency values of both agonists. We conclude that trandolapril treatment decreased the carotid arterial reactivity in normotensive rats and that this effect is endothelium-dependent. Furthermore, the involvement of B(2)-receptors and NO production, but not of prostaglandins, is suggested in this mechanism.
- Published
- 2006
- Full Text
- View/download PDF
27. Inhibitory effects of atropine and hexamethonium on the angiotensin II-induced contractions of rat anococcygeus smooth muscles.
- Author
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de Godoy MA, Accorsi-Mendonça D, and de Oliveira AM
- Subjects
- Angiotensin II physiology, Animals, Atropine administration & dosage, Cholinesterase Inhibitors pharmacology, Depression, Chemical, Dose-Response Relationship, Drug, In Vitro Techniques, Male, Muscarinic Antagonists pharmacology, Muscle Contraction drug effects, Muscle, Smooth physiology, NG-Nitroarginine Methyl Ester pharmacology, Neostigmine pharmacology, Nicotinic Antagonists pharmacology, Rats, Rats, Wistar, Yohimbine pharmacology, Angiotensin II pharmacology, Atropine pharmacology, Cholinergic Antagonists pharmacology, Hexamethonium pharmacology, Muscle, Smooth drug effects, Vasoconstrictor Agents pharmacology
- Abstract
We have evaluated the interaction between angiotensin II (Ang II) and the cholinergic transmission in anococcygeus smooth muscles isolated from rats treated (sympathectomised group) or not (vehicle group) with reserpine and alpha-methyl-p-tyrosine. For this, we contracted the tissues with Ang II in the presence and absence of atropine and hexamethonium. Ang II induced concentration-dependent contractions, which did not undergo temporal changes in tissues isolated from both groups of rats. In the vehicle group, Ang II induced more potent contractions than in the sympathectomised group. In the sympathectomised rat group, atropine inhibited the contractions induced by Ang II in a concentration-dependent fashion with no decrease in E(max). Additionally, hexamethonium inhibited the contraction induced by Ang II in a concentration-dependent fashion with a decrease in E(max). Association of atropine and hexamethonium produced Ang II-induced curves with rightward shifts from the control curve with a decrease in E(max). Incubation with N(G)-nitro-L-arginine methyl ester (L-NAME) reversed the effects of atropine and hexamethonium association. Conversely, in the vehicle group of rats, atropine and hexamethonium did not produce any significant effect. However, in the presence of yohimbine, atropine shifted the Ang II-induced curves to the right of the control curve with no E(max) decrease. Results suggest that there is a positive interaction between Ang II and cholinergic transmission in the rat anococcygeus smooth muscle mediated by angiotensin receptors located on pre-ganglionic cells.
- Published
- 2003
- Full Text
- View/download PDF
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