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Benedito H Machado - One of the best experts on this subject based on the ideXlab platform.

  • inhibitory modulation of chemoreflex Bradycardia by stimulation of the nucleus raphe obscurus is mediated by 5 ht3 receptors in the nts of awake rats
    Autonomic Neuroscience: Basic and Clinical, 2007
    Co-Authors: Karin Viana Weissheimer, Benedito H Machado
    Abstract:

    Several studies demonstrated the involvement of 5-hydroxytryptamine (5-HT) and its different receptor subtypes in the modulation of neurotransmission of cardiovascular reflexes in the nucleus tractus solitarii (NTS). Moreover, anatomic evidence suggests that nucleus raphe obscurus (ROb) is a source of 5-HT-containing terminals within the NTS. In the present study we investigated the possible changes in the cardiovascular responses to peripheral chemoreceptor activation by potassium cyanide (KCN, i.v.) following ROb stimulation with L-glutamate (10 nmol/50 nL) and also whether 5-HT3 receptors in the caudal commissural NTS are involved in this neuromodulation. The results showed that stimulation of the ROb with L-glutamate in awake rats (n=15) produced a significant reduction in the bradycardic response 30 s after the microinjection (-182+/-19 vs -236+/-10 bpm; Wilcoxon test) but no changes in the pressor response to peripheral chemoreceptor activation (43+/-4 vs 51+/-3 mmHg; two-way ANOVA) in relation to the control. Microinjection of 5--HT3 receptors antagonist granisetron (500 pmol/50 nL), but not the vehicle, into the caudal commissural NTS bilaterally prevented the reduction of chemoreflex Bradycardia in response to microinjection of L-glutamate into ROb. These data indicate that 5-HT-containing projections from ROb to the NTS play an inhibitory neuromodulatory role in the chemoreflex evoked Bradycardia by releasing 5-HT and activating 5-HT3 receptors in the caudal NTS.

  • Sensory Afferent Selective Role of P2 Receptors in the Nucleus Tractus Solitarii for Mediating the Cardiac Component of the Peripheral Chemoreceptor Reflex in Rats
    The Journal of Physiology, 2002
    Co-Authors: Julian F. R. Paton, Patricia M. De Paula, K. Michael Spyer, Benedito H Machado, Pedro Boscan
    Abstract:

    We have assessed the functional role of type 2 purinergic (P2) receptors within the caudal aspect of the commissural nucleus tractus solitarii (NTS) in mediating the peripheral chemoreceptor reflex cardiorespiratory response in the arterially perfused in situ working heart-brainstem preparation of rats. Microinjection in NTS of either suramin (100 pmol) or pyrinoxalphosphate-6-azophenyl-2′,4′-disulphonic acid tetrasodium salt (PPADS; 10 pmol) depressed the reflex Bradycardia (by ≈50 %), but not the tachypnoea, following peripheral chemoreceptor stimulation. In contrast, the reflex Bradycardia produced by stimulation of pharyngo-oesophageal receptors was unaffected. Furthermore, microinjections in NTS of the P2X receptor agonist α,β-methyleneadenosine 5′-triphosphate (10 pmol) evoked a Bradycardia which was antagonized by suramin (100 pmol). This P2X agonist reversibly potentiated the peripheral chemoreceptor-evoked Bradycardia. The effect of suramin was selective to purinergic receptors because the Bradycardia evoked by microinjection of α,β-methyleneadenosine 5′-triphosphate was blocked while the bradycardic responses to microinjections of NMDA or non-NMDA receptor agonists were not affected. From whole-cell recordings, some NTS neurones received convergent excitatory synaptic inputs from both peripheral chemoreceptors and receptors at the pharyngo-oesophageal junction. The excitatory postsynaptic response evoked by chemoreceptor stimulation was depressed by suramin, but convergent excitatory inputs from pharyngo-oesophageal receptors were unperturbed. Our findings support the hypothesis that caudal commissural NTS P2 purinergic receptors play a role in the neurotransmission of the parasympathetic (bradycardic) component of the chemoreceptor reflex. This effect is highly selective in that the chemoreceptor afferent-evoked tachypnoea, as well as other visceral receptor-mediated reflex Bradycardia, remain unaffected.

  • bradycardic and hypotensive responses to microinjection of l glutamate into the lateral aspect of the commissural nts are blocked by an nmda receptor antagonist
    Brain Research, 2000
    Co-Authors: R O Canesin, L. G. H. Bonagamba, Benedito H Machado
    Abstract:

    Abstract Baroreflex activation by phenylephrine infusion produces a bradycardic response while microinjection of l -glutamate into the most lateral aspect of the commissural nucleus tractus solitarius (NTS, 0.8 mm lateral to the midline) produces bradycardic and hypotensive responses. In the present study we investigated the role of NMDA receptors in the lateral aspect of the commissural NTS (0.8 mm lateral to the midline) in the bradycardic and hypotensive responses to microinjection of l -glutamate as well as in the processing of the bradycardic response to the baroreflex activation. The hypotensive and bradycardic responses to l -glutamate microinjection into the NTS were blocked by methyl-atropine (intravenous, i.v.), indicating that the hypotensive response was secondary to the Bradycardia. Microinjection of l -glutamate (1 nmol/50 nl) into the NTS was performed before and after microinjection of increasing doses of phosphonovaleric acid (AP-5, a selective NMDA antagonist) at the same site. The microinjection of AP-5 [0.5 ( n =9), 2.0 ( n =8) and 10.0 nmol/50 nl ( n =7)] into the NTS (0.8 mm lateral to the midline) produced a dose-dependent blockade of the bradycardic and hypotensive responses to l -glutamate. In a specific group of rats the microinjection of 10 nmol/50 nl of AP-5 produced a significant reduction in baroreflex sensitivity 2 min after microinjection into the lateral NTS [gain=−1.48±0.12 vs. −0.5±0.2 beats/mmHg, ( n =5)], which was reversible. The data show that the bradycardic responses produced by microinjection of l -glutamate into the most lateral aspect of the commissural NTS or by activation of the baroreflex were blocked by microinjection of AP-5, indicating that the neurotransmission of the parasympathetic component of the baroreflex in the neurons of the lateral aspect of the commissural NTS involves NMDA receptors.

  • NMDA receptors in NTS are involved in bradycardic but not in pressor response of chemoreflex
    American Journal of Physiology-heart and Circulatory Physiology, 1995
    Co-Authors: Andrea Siqueira Haibara, Deoclécio A. Chianca, L. G. H. Bonagamba, Eduardo Colombari, Benedito H Machado
    Abstract:

    Activation of carotid chemoreceptors with intravenous potassium cyanide (KCN) produces increases in arterial pressure, Bradycardia, and tachypnea. In the present study, we activated carotid chemoreceptors with KCN and the neurotransmission of the chemoreceptor reflex into the commissural nucleus tractus solitarii (NTS) was blocked with phosphonovaleric acid (AP-5), an N-methyl-D-aspartate (NMDA)-selective antagonist. The aim of this study was to evaluate the involvement of NMDA receptors in the cardiovascular and respiratory responses produced by chemoreceptor activation in unanesthetized rats. The pressor response to KCN was not changed after microinjection of three different doses of AP-5 into the NTS, whereas the bradycardic response was reduced in a dose-dependent manner. The increase in respiratory frequency in response to carotid chemoreceptor activation was also not affected by AP-5 microinjected into the NTS. The data indicate that the activation of the cardiovagal component of the chemoreflex in the commissural NTS is mediated by NMDA receptors, whereas pressor and ventilatory responses are not.

Florence Netzer - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of the bradycardic component of the von bezold jarisch reflex and carotid chemoreceptor reflex by periaqueductal gray stimulation involvement of medullary receptors
    European Journal of Neuroscience, 2009
    Co-Authors: Florence Netzer, Nathalie Mandjee, Jeanfrancois Bernard, Raul Laguzzi, Michel Hamon, Anthony J M Verberne, Caroline Sevozcouche
    Abstract:

    : Stimulation of the dorsolateral periaqueductal gray matter (dlPAG) and the B3 cell group inhibits the cardiovagal component of the baroreflex in rats. Our aim was to determine whether the defence reaction induces similar modulatory effects on the cardiac response of the von Bezold-Jarisch reflex and the carotid chemoreceptor reflex. We examined the effects of dlPAG stimulation on the reflex Bradycardia triggered by systemic administration of phenylbiguanide or potassium cyanide. Electrical and chemical stimulation of the dlPAG produced marked inhibition of the cardiovagal components of the von Bezold-Jarisch and the carotid chemoreceptor reflexes. In addition, as 5-HT(3), NK(1) and GABA(A) receptor activation blocks cardiac reflex responses, we studied whether these receptors were involved in the dlPAG-induced inhibitory effects. We found that, after microinjection of granisetron (a 5-HT(3) receptor antagonist), bicuculline (a GABA(A) receptor antagonist) and GR-205171 (an NK(1) receptor antagonist) into the nucleus of the solitary tract (NTS), reflex bradycardic responses were preserved during dlPAG stimulation. Finally, activation of the B3 region also inhibited both reflex bradycardic responses, and these effects were prevented by prior blockade of 5-HT(3) receptors in the NTS. The inhibitory effect of dlPAG stimulation on the cardiac reflex responses was prevented by inhibition of neurons in the medullary B3 region. In conclusion, 5-HT(3), GABA(A) and NK(1) receptors in the NTS appear to be involved in the inhibition of the von Bezold-Jarisch reflex and the carotid chemoreceptor reflex Bradycardia evoked by activation of neurons in the dlPAG and the raphe magnus.

Correa, Fernando M. A. - One of the best experts on this subject based on the ideXlab platform.

  • Bed nucleus of the stria terminalis alpha(1)-adrenoceptor modulates baroreflex cardiac component in unanesthetized rats
    ELSEVIER SCIENCE BV, 2008
    Co-Authors: Crestani, Carlos C., Alves, Fernando H. F., Resstel, Leonardo B. M., Correa, Fernando M. A.
    Abstract:

    The bed nucleus of stria terminalis (BST) has a tonic modulating role on the baroreflex parasympathetic component. In the present study, we verified that local BST-adrenoceptors modulate baroreflex-evoked Bradycardiac responses in unanesthetized rats. Bilateral microinjection of the selective alpha(1)-adrenoceptor antagonist WB4101 (15 nmol/100 nL) into the BST increased the gain of reflex Bradycardia in response to mean arterial pressure increases caused by intravenous (i.v.) infusion of phenylephrine, suggesting that BST alpha(1)-adrenoceptors modulate baroreflex Bradycardiac response. Bilateral microinjection of either the selective alpha(2)-adrenoceptor antagonist RX821002 (15 nmol/100 nL) or the non-selective beta-adrenoceptor antagonist propranolol (15 nmol/100 nL) into the BST had not affected baroreflex Bradycardia. Animals were pretreated intravenously with the cholinergic muscarinic receptor antagonist homatropine methyl bromide (HMB, 1.5 mg/Kg) to test the hypothesis that activation of alpha(1)-adrenoceptors in the BST would modulate the baroreflex parasympathetic component. Baroreflex Bradycardiac responses evoked before and after BST treatment with WB4101 were no longer different when rats were pretreated with HMB. These results suggest that parasympathetic activation accounts for the effects saw after BST pharmacological manipulation and ruling out the possibility of a sympathetic withdraw. In conclusion, our data point out that local alpha(1)-adrenoceptors mediate the BST tonic influence on the baroreflex Bradycardiac response modulating parasympathetic cardiac activity. (C) 2008 Elsevier B.V. All rights reserved

  • Bed nucleus of the stria terminalis alpha(1)-adrenoceptor modulates baroreflex cardiac component in unanesthetized rats
    ELSEVIER SCIENCE BV, 2008
    Co-Authors: Crestani, Carlos C., Alves, Fernando H. F., Resstel, Leonardo B. M., Correa, Fernando M. A.
    Abstract:

    The bed nucleus of stria terminalis (BST) has a tonic modulating role on the baroreflex parasympathetic component. In the present study, we verified that local BST-adrenoceptors modulate baroreflex-evoked Bradycardiac responses in unanesthetized rats. Bilateral microinjection of the selective alpha(1)-adrenoceptor antagonist WB4101 (15 nmol/100 nL) into the BST increased the gain of reflex Bradycardia in response to mean arterial pressure increases caused by intravenous (i.v.) infusion of phenylephrine, suggesting that BST alpha(1)-adrenoceptors modulate baroreflex Bradycardiac response. Bilateral microinjection of either the selective alpha(2)-adrenoceptor antagonist RX821002 (15 nmol/100 nL) or the non-selective beta-adrenoceptor antagonist propranolol (15 nmol/100 nL) into the BST had not affected baroreflex Bradycardia. Animals were pretreated intravenously with the cholinergic muscarinic receptor antagonist homatropine methyl bromide (HMB, 1.5 mg/Kg) to test the hypothesis that activation of alpha(1)-adrenoceptors in the BST would modulate the baroreflex parasympathetic component. Baroreflex Bradycardiac responses evoked before and after BST treatment with WB4101 were no longer different when rats were pretreated with HMB. These results suggest that parasympathetic activation accounts for the effects saw after BST pharmacological manipulation and ruling out the possibility of a sympathetic withdraw. In conclusion, our data point out that local alpha(1)-adrenoceptors mediate the BST tonic influence on the baroreflex Bradycardiac response modulating parasympathetic cardiac activity. (C) 2008 Elsevier B.V. All rights reserved.FAPESP[06/57670-4]CNPq[870307/1997-5]CNPq[306381/2003-6]CNPq[505394/2003-0]FAEP

Caroline Sevozcouche - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of the bradycardic component of the von bezold jarisch reflex and carotid chemoreceptor reflex by periaqueductal gray stimulation involvement of medullary receptors
    European Journal of Neuroscience, 2009
    Co-Authors: Florence Netzer, Nathalie Mandjee, Jeanfrancois Bernard, Raul Laguzzi, Michel Hamon, Anthony J M Verberne, Caroline Sevozcouche
    Abstract:

    : Stimulation of the dorsolateral periaqueductal gray matter (dlPAG) and the B3 cell group inhibits the cardiovagal component of the baroreflex in rats. Our aim was to determine whether the defence reaction induces similar modulatory effects on the cardiac response of the von Bezold-Jarisch reflex and the carotid chemoreceptor reflex. We examined the effects of dlPAG stimulation on the reflex Bradycardia triggered by systemic administration of phenylbiguanide or potassium cyanide. Electrical and chemical stimulation of the dlPAG produced marked inhibition of the cardiovagal components of the von Bezold-Jarisch and the carotid chemoreceptor reflexes. In addition, as 5-HT(3), NK(1) and GABA(A) receptor activation blocks cardiac reflex responses, we studied whether these receptors were involved in the dlPAG-induced inhibitory effects. We found that, after microinjection of granisetron (a 5-HT(3) receptor antagonist), bicuculline (a GABA(A) receptor antagonist) and GR-205171 (an NK(1) receptor antagonist) into the nucleus of the solitary tract (NTS), reflex bradycardic responses were preserved during dlPAG stimulation. Finally, activation of the B3 region also inhibited both reflex bradycardic responses, and these effects were prevented by prior blockade of 5-HT(3) receptors in the NTS. The inhibitory effect of dlPAG stimulation on the cardiac reflex responses was prevented by inhibition of neurons in the medullary B3 region. In conclusion, 5-HT(3), GABA(A) and NK(1) receptors in the NTS appear to be involved in the inhibition of the von Bezold-Jarisch reflex and the carotid chemoreceptor reflex Bradycardia evoked by activation of neurons in the dlPAG and the raphe magnus.

Julian F. R. Paton - One of the best experts on this subject based on the ideXlab platform.

  • involvement of the purinergic system in central cardiovascular modulation at the level of the nucleus ambiguus of anaesthetized rats
    Experimental Physiology, 2011
    Co-Authors: Luciana Mesquita Passamani, Julian F. R. Paton, H Mauad, Diego Franca Pedrosa, Luiz Carlos Schenberg, Karla Nívea Sampaio
    Abstract:

    Anatomical studies have demonstrated the existence of purinergic P2 receptors in the nucleus ambiguus (NA), a site containing cardiac vagal motoneurons. However, very little is known about the functional role of these receptors in central cardiac vagal regulation. The aims of our study were to evaluate the following: (1) the blood pressure and heart rate responses following purinoceptor activation within the NA; (2) the role of purinoceptors and excitatory amino acid (EAA) receptors in mediating the cardiovascular responses evoked by ATP and L-glutamate stimulation of NA; and (3) the role of NA purinoceptors in mediating the cardiovascular responses of the Bezold-Jarisch reflex. In anaesthetized rats, microinjection of L-glutamate (5.0 nmol/50 nl) into the NA induced a marked and immediate onset Bradycardia with minimal change in arterial pressure. Microinjection of ATP into the NA induced a dose-dependent (0.31-6.0 nmol/50 nl) Bradycardia and pressor responses. It is noteworthy that the Bradycardia occurred either before or simultaneously with a pressor response (when present), indicating that it was not a baroreceptor reflex mediated response due to the rise in arterial pressure. The pressor response was prevented by α(1)-adrenergic blockade with prazosin, whereas muscarinic blockade with methyl-atropine abolished the evoked Bradycardia. Ipsilateral microinjection of PPADS (a P2 receptor antagonist; 500 pmol/100 nl) into the NA significantly attenuated the ATP-induced Bradycardia but spared the pressor response. In contrast, PPADS in the NA had no effect on the L-glutamate-evoked bradycardic response. Ipsilateral injection of kynurenic acid (a non-selective EAA receptor antagonist; 10 nmol/50 nl) into the NA totally blocked the Bradycardia induced by l-glutamate and partly attenuated the ATP induced Bradycardia. Finally, both the depressor and the bradycardic responses of the Bezold-Jarisch reflex were attenuated significantly (P < 0.01 and P < 0.05, respectively) following bilateral microinjection of PPADS into the NA. These results identify ATP and purinergic P2 receptors within the ventrolateral medulla as excitatory to cardiovagal neurons. Additionally, our data show that P2 receptors within the ventrolateral medulla are integral to the cardiovascular responses of the Bezold-Jarisch reflex.

  • Sensory Afferent Selective Role of P2 Receptors in the Nucleus Tractus Solitarii for Mediating the Cardiac Component of the Peripheral Chemoreceptor Reflex in Rats
    The Journal of Physiology, 2002
    Co-Authors: Julian F. R. Paton, Patricia M. De Paula, K. Michael Spyer, Benedito H Machado, Pedro Boscan
    Abstract:

    We have assessed the functional role of type 2 purinergic (P2) receptors within the caudal aspect of the commissural nucleus tractus solitarii (NTS) in mediating the peripheral chemoreceptor reflex cardiorespiratory response in the arterially perfused in situ working heart-brainstem preparation of rats. Microinjection in NTS of either suramin (100 pmol) or pyrinoxalphosphate-6-azophenyl-2′,4′-disulphonic acid tetrasodium salt (PPADS; 10 pmol) depressed the reflex Bradycardia (by ≈50 %), but not the tachypnoea, following peripheral chemoreceptor stimulation. In contrast, the reflex Bradycardia produced by stimulation of pharyngo-oesophageal receptors was unaffected. Furthermore, microinjections in NTS of the P2X receptor agonist α,β-methyleneadenosine 5′-triphosphate (10 pmol) evoked a Bradycardia which was antagonized by suramin (100 pmol). This P2X agonist reversibly potentiated the peripheral chemoreceptor-evoked Bradycardia. The effect of suramin was selective to purinergic receptors because the Bradycardia evoked by microinjection of α,β-methyleneadenosine 5′-triphosphate was blocked while the bradycardic responses to microinjections of NMDA or non-NMDA receptor agonists were not affected. From whole-cell recordings, some NTS neurones received convergent excitatory synaptic inputs from both peripheral chemoreceptors and receptors at the pharyngo-oesophageal junction. The excitatory postsynaptic response evoked by chemoreceptor stimulation was depressed by suramin, but convergent excitatory inputs from pharyngo-oesophageal receptors were unperturbed. Our findings support the hypothesis that caudal commissural NTS P2 purinergic receptors play a role in the neurotransmission of the parasympathetic (bradycardic) component of the chemoreceptor reflex. This effect is highly selective in that the chemoreceptor afferent-evoked tachypnoea, as well as other visceral receptor-mediated reflex Bradycardia, remain unaffected.