Mirela B Dias

Universidade Federal de Goiás, Goianá, Goiás, Brazil

Are you Mirela B Dias?

Claim your profile

Publications (13)40.8 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: AIM: Central chemoreceptors are important to detect changes of CO(2) /H(+) , and the Locus coeruleus (LC) is one of the many putative central chemoreceptor sites. Here, we studied the contribution of LC glutamatergic receptors on ventilatory, cardiovascular and thermal responses to hypercapnia. METHODS: To this end, we determined pulmonary ventilation ($${\rm{\dot VE}}$$), body temperatures (Tb), mean arterial pressure (MAP) and heart rate (fH) of male Wistar rats before and after unilateral microinjection of Kynurenic Acid (KY, an ionotropic glutamate receptor antagonist, 10 nmol/0.1 μL) or α-methyl-4-carboxyphenylglycine (MCPG, a metabotropic glutamate receptor antagonist, 10 nmol/0.1 μL) into the LC, followed by 60 minutes of air breathing or hypercapnia exposure (7% CO(2) ). RESULTS: Ventilatory response to hypercapnia was higher in animals treated with KY intra-LC (1918.7 ± 275.4) compared with the control group (1057.8 ± 213.9, P < 0.01). However, the MCPG treatment within the LC had no effect on the hypercapnia-induced hyperpnea. The cardiovascular and thermal controls were not affected by hypercapnia or by the injection of KY and MCPG in the LC. CONCLUSION: These data suggest that glutamate acting on ionotropic, but not metabotropic, receptors in the LC exerts an inhibitory modulation of hypercapnia-induced hyperpnea. Acta Physiologica © 2013 Scandinavian Physiological Society.
    Acta Physiologica 02/2013; · 4.38 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: The medullary raphe (MR) is a putative central chemoreceptor site, contributing to hypercapnic respiratory responses elicited by changes in brain PCO(2)/pH. Purinergic mechanisms in the central nervous system appear to contribute to central chemosensitivity. To further explore the role of P2 receptors within the rostral and caudal MR in relation to respiratory control in room air and hypercapnic conditions, we performed microinjections of PPADS, a non-selective P2X antagonist, in conscious rats. Microinjections of PPADS into the rostral or caudal MR produced no changes in the respiratory frequency, tidal volume and ventilation in room air condition. The ventilatory response to hypercapnia was attenuated after microinjection of PPADS into the rostral but not in the caudal MR when compared to the control group (vehicle microinjection). These data suggest that P2X receptors in the rostral MR contribute to the ventilatory response to CO(2), but do not participate in the tonic maintenance of ventilation under room air condition in conscious rats.
    Respiratory Physiology & Neurobiology 07/2012; 184(1):41-7. · 2.05 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Central mechanisms of coupling between respiratory and sympathetic systems are essential for the entrainment between the enhanced respiratory drive and sympathoexcitation in response to hypoxia. However, the brainstem nuclei and neuronal network involved in these respiratory-sympathetic interactions remain unclear. Here, we evaluated whether the increase in expiratory activity and expiratory-modulated sympathoexcitation produced by the peripheral chemoreflex activation involves the retrotrapezoid nucleus/parafacial respiratory region (RTN/pFRG). Using decerebrated arterially perfused in situ rat preparations (60-80 g), we recorded the activities of thoracic sympathetic (tSN), phrenic (PN), and abdominal nerves (AbN) as well as the extracellular activity of RTN/pFRG expiratory neurons, and reflex responses to chemoreflex activation were evaluated before and after inactivation of the RTN/pFRG region with muscimol (1 mM). In the RTN/pFRG, we identified late-expiratory (late-E) neurons (n = 5) that were silent at resting but fired coincidently with the emergence of late-E bursts in AbN after peripheral chemoreceptor activation. Bilateral muscimol microinjections into the RTN/pFRG region (n = 6) significantly reduced basal PN frequency, mean AbN activity, and the amplitude of respiratory modulation of tSN (P < 0.05). With respect to peripheral chemoreflex responses, muscimol microinjections in the RTN/pFRG enhanced the PN inspiratory response, abolished the evoked late-E activity of AbN, but did not alter either the magnitude or pattern of the tSN reflex response. These findings indicate that the RTN/pFRG region is critically involved in the processing of the active expiratory response but not of the expiratory-modulated sympathetic response to peripheral chemoreflex activation of rat in situ preparations.
    Journal of Neurophysiology 05/2012; 108(3):882-90. · 3.30 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Serotonergic (5-HT) neurons in the nucleus raphe obscurus (ROb) are involved in the respiratory control network. However, it is not known whether ROb 5-HT neurons play a role in the functional interdependence between central and peripheral chemoreceptors. Therefore, we investigated the role of ROb 5-HT neurons in the ventilatory responses to CO₂ and their putative involvement in the central-peripheral CO₂ chemoreceptor interaction in unanaesthetised rats. We used a chemical lesion specific for 5-HT neurons (anti-SERT-SAP) of the ROb in animals with the carotid body (CB) intact or removed (CBR). Pulmonary ventilation (V (E)), body temperature and the arterial blood gases were measured before, during and after a hypercapnic challenge (7% CO₂). The lesion of ROb 5-HT neurons alone (CB intact) or the lesion of 5-HT neurons of ROb+CBR did not affect baseline V (E) during normocapnic condition. Killing ROb 5-HT neurons (CB intact) significantly decreased the ventilatory response to hypercapnia (p < 0.05). The reduction in CO₂ sensitivity was approximately 15%. When ROb 5-HT neurons lesion was combined with CBR (anti-SERT-SAP+CBR), the V (E) response to hypercapnia was further decreased (-31.2%) compared to the control group. The attenuation of CO₂ sensitivity was approximately 30%, and it was more pronounced than the sum of the individual effects of central (ROb lesion; -12.3%) or peripheral (CBR; -5.5%) treatments. Our data indicate that ROb 5-HT neurons play an important role in the CO₂ drive to breathing and may act as an important element in the central-peripheral chemoreception interaction to CO₂ responsiveness.
    Pflügers Archiv - European Journal of Physiology 09/2011; 462(3):407-18. · 4.87 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: It has been suggested that the medullary raphe (MR) plays a key role in the physiological responses to hypoxia. As opioid μ-receptors have been found in the MR, we studied the putative role of opioid μ-receptors in the rostral MR (rMR) region on ventilation in normal and 7% hypoxic conditions. We measured pulmonary ventilation (VE) and the body temperatures (Tb) of male Wistar rats before and after the selective opioid μ-receptor antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, cyclic, 0.1 μg per 0.1 μL) was microinjected into the rMR during normoxia or after 60 min of hypoxia. The animals treated with intra-rMR CTAP exhibited an attenuation of the ventilatory response to hypoxia (430 ± 86 mL kg(-1) min(-1)) compared with the control group (790 ± 82 mL kg(-1) min(-1) ) (P < 0.05). No differences in the Tb were observed between groups during hypoxia. These data suggest that opioids acting on μ-receptors in the rMR exert an excitatory modulation of hyperventilation induced by hypoxia.
    Acta Physiologica 08/2011; 204(3):435-42. · 4.38 Impact Factor
  • Autonomic Neuroscience-basic & Clinical - AUTON NEUROSCI-BASIC CLIN. 01/2011; 163(1):115-115.
  • [show abstract] [hide abstract]
    ABSTRACT: It has been suggested that the medullary raphe (MR) plays a key role in the physiological responses to hypoxia and hypercapnia. We assessed the role of ionotropic glutamate receptors in the rostral MR (rMR) in the respiratory responses to hypoxia and hypercapnia by measuring pulmonary ventilation (V.(E)) and body temperature (Tb) of male Wistar rats before and after microinjecting Kynurenic acid (KY, an ionotropic glutamate receptors antagonist, 0.1mM) into the rMR followed by 60 min of hypoxia (7% O₂) or hypercapnia exposure (7% CO₂). Compared to the control group, the ventilatory response to hypoxia was attenuated in animals treated with KY intra-rMR, however the ventilatory response to hypercapnia increased significantly. No differences in Tb among groups were observed during hypoxia or hypercapnia. These data suggest that the glutamate acting on ionotropic receptors in the rMR exerts an excitatory modulation on hyperventilation induced by hypoxia but an inhibitory modulation on the hypercapnia-induced hyperpnea.
    Respiratory Physiology & Neurobiology 09/2010; 175(1):104-11. · 2.05 Impact Factor
  • Source
    Mirela Barros Dias, Aihua Li, Eugene Nattie
    [show abstract] [hide abstract]
    ABSTRACT: It has been shown that orexin plays an important role in the hypercapnic chemoreflex during wakefulness, and OX(1)Rs in the retrotrapezoid nucleus (RTN) participate in this mechanism. We hypothesized that OX(1)R in the rostral medullary raphe (MR) also contributes to the hypercapnic chemoreflex. We studied the effects on ventilation in air and in 7% CO(2) of focal antagonism of OX(1)R in the rostral MR by microdialysis of SB-334867 in rats during wakefulness and NREM sleep, under dark and light periods. During wakefulness in the dark period, but not in the light period, SB-334867 caused a 16% reduction of the hyperventilation induced by 7% CO(2) compared with vehicle. There was no significant effect in sleep. The basal ventilation, body temperature and V(O2) were not affected. No effect was observed in a separate group of animals which had the microdialysis probe misplaced (peri-raphe). We conclude that OX(1)R in the rostral medullary raphe contribute to the hypercapnic chemoreflex in wakefulness, during the dark period in rats.
    Respiratory Physiology & Neurobiology 12/2009; 170(1):96-102. · 2.05 Impact Factor
  • Source
    Mirela Barros Dias, Aihua Li, Eugene E Nattie
    [show abstract] [hide abstract]
    ABSTRACT: Recent data from transgenic mice suggest that orexin plays an important role in the ventilatory response to CO(2) during wakefulness. We hypothesized that orexin receptor-1 (OX(1)R) in the retrotrapezoid nucleus (RTN) contributes to chemoreception. In unanaesthetized rats, we measured ventilation using a whole-body plethysmograph, together with EEG and EMG. We dialysed the vehicle and then SB-334867 (OX(1)R antagonist) into the RTN to focally inhibit OX(1)R and studied the effects of both treatments on breathing in air and in 7% CO(2). During wakefulness, SB-334867 caused a 30% reduction of the hyperventilation induced by 7% CO(2) (mean +/- S.E.M., 135 +/- 10 ml (100 g)(-1) min(-1)) compared with vehicle (182 +/- 10 ml (100 g)(-1) min(-1)) (P < 0.01). This effect was due to both decreased tidal volume and breathing frequency. There was a much smaller, though significant, effect in sleep (9% reduction). Neither basal ventilation nor oxygen consumption was affected. The number and duration of apnoeas were similar between control and treatment periods. No effect was observed in a separate group of animals who had the microdialysis probe misplaced (peri-RTN). We conclude that projections of orexin-containing neurons to the RTN contribute, via OX(1)Rs in the region, to the hypercapnic chemoreflex control during wakefulness and to a lesser extent, non-rapid eye movement sleep.
    The Journal of Physiology 03/2009; 587(Pt 9):2059-67. · 4.38 Impact Factor
  • Source
    Mirela Barros Dias, Aihua Li, Eugene Nattie
    [show abstract] [hide abstract]
    ABSTRACT: Simultaneous inhibition of the retrotrapezoid nucleus (RTN) and raphe obscurus (ROb) decreased the systemic CO(2) response by 51%, an effect greater than inhibition of RTN (-24%) or ROb (0%) alone, suggesting that ROb modulates chemoreception by interaction with the RTN (19). We investigated this interaction further by simultaneous dialysis of artificial cerebrospinal fluid equilibrated with 25% CO(2) in two probes located in or adjacent to the RTN and ROb in conscious adult male rats. Ventilation was measured in a whole body plethysmograph at 30 degrees C. There were four groups (n = 5): 1) probes correctly placed in both RTN and ROb (RTN-ROb); 2) one probe correctly placed in RTN and one incorrectly placed in areas adjacent to ROb (RTN-peri-ROb); 3) one probe correctly placed in ROb and one probe incorrectly placed in areas adjacent to RTN (peri-RTN-ROb); and 4) neither probe correctly placed (peri-RTN-peri-ROb). Focal simultaneous acidification of RTN-ROb significantly increased ventilation (Ve) up to 22% compared with baseline, with significant increases in both breathing frequency and tidal volume. Focal acidification of RTN-peri-ROb increased Ve significantly by up to 15% compared with baseline. Focal acidification of ROb and peri-RTN had no significant effect. The simultaneous acidification of regions just outside the RTN and ROb actually decreased Ve by up to 11%. These results support a modulatory role for the ROb with respect to central chemoreception at the RTN.
    Journal of Applied Physiology 08/2008; 105(1):83-90. · 3.48 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: There is evidence that serotonin [5-hydroxytryptamine (5-HT)] is involved in the physiological responses to hypercapnia. Serotonergic neurons represent the major cell type (comprising 15-20% of the neurons) in raphe magnus nucleus (RMg), which is a medullary raphe nucleus. In the present study, we tested the hypothesis 1) that RMg plays a role in the ventilatory and thermal responses to hypercapnia, and 2) that RMg serotonergic neurons are involved in these responses. To this end, we microinjected 1) ibotenic acid to promote nonspecific lesioning of neurons in the RMg, or 2) anti-SERT-SAP (an immunotoxin that utilizes a monoclonal antibody to the third extracellular domain of the serotonin reuptake transporter) to specifically kill the serotonergic neurons in the RMg. Hypercapnia caused hyperventilation and hypothermia in all groups. RMg nonspecific lesions elicited a significant reduction of the ventilatory response to hypercapnia due to lower tidal volume (Vt) and respiratory frequency. Rats submitted to specific killing of RMg serotonergic neurons showed no consistent difference in ventilation during air breathing but had a decreased ventilatory response to CO(2) due to lower Vt. The hypercapnia-induced hypothermia was not affected by specific or nonspecific lesions of RMg serotonergic neurons. These data suggest that RMg serotonergic neurons do not participate in the tonic maintenance of ventilation during air breathing but contribute to the ventilatory response to CO(2). Ultimately, this nucleus may not be involved in the thermal responses to CO(2).
    Journal of Applied Physiology 12/2007; 103(5):1780-8. · 3.48 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Recently, heme oxygenase-carbon monoxide (HO-CO) pathway has been reported to be involved in the development of lipopolysaccharide (LPS) fever. However, no information exists about its participation in LPS tolerance, which is defined by an attenuation of the febrile response to repeated administrations of LPS. Thus, we tested the hypothesis that HO-CO pathway plays a role in endotoxin tolerance, which was induced by means of three consecutive LPS intraperitoneal injections (i.p.) at 24-h intervals. Body temperature (Tb) was measured by biotelemetry. Induction of the HO pathway using intracerebroventricular (i.c.v.) heme lysinate reversed tolerance, and this effect could be prevented by pretreatment with ODQ [a soluble guanylate cyclase (sGC) inhibitor; i.c.v.]. These results indicate that HO-CO pathway seems to be down-regulated during LPS tolerance, and that CO is the HO product that can prevent LPS tolerance, acting via cGMP. In further support, either biliverdine or iron (the others HO products; i.c.v.) had no effect in LPS-induced tolerance.
    Brain Research 10/2006; 1111(1):83-9. · 2.88 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: The injection of repeated doses of lipopolysaccharide (LPS) results in attenuation of the febrile response, which is called endotoxin tolerance. We tested the hypothesis that nitric oxide (NO) arising from inducible NO synthase (iNOS) plays a role in endotoxin tolerance, using not only pharmacological trials but also genetically engineered mice. Body core temperature was measured by biotelemetry in mice treated with NG-monomethyl-L-arginine (L-NMMA, 40 mg/kg; a nonselective NO synthase inhibitor) or aminoguanidine (AG, 10 mg/kg; a selective iNOS inhibitor) and in mice deficient in the iNOS gene (iNOS KO) mice. Tolerance to LPS was induced by means of three consecutive LPS (100 microg/kg) intraperitoneal injections at 24-h intervals. In wild-type mice, we observed a significant reduction of the febrile response to repeated administration of LPS. Injection of L-NMMA and AG markedly enhanced the febrile response to LPS in tolerant animals. Conversely, iNOS-KO mice repeatedly injected with LPS did not become tolerant to the pyrogenic effect of LPS. These data are consistent with the notion that NO modulates LPS tolerance in mice and that iNOS isoform is involved in NO synthesis during LPS tolerance.
    Journal of Applied Physiology 05/2005; 98(4):1322-7. · 3.48 Impact Factor

Publication Stats

130 Citations
4 Downloads
631 Views
40.80 Total Impact Points

Institutions

  • 2010–2012
    • Universidade Federal de Goiás
      Goianá, Goiás, Brazil
  • 2009
    • Dartmouth Medical School
      • Department of Physiology and Neurobiology
      Hanover, NH, United States
  • 2005–2008
    • University of São Paulo
      • Faculdade de Medicina de Ribeirão Preto (FMRP)
      São Paulo, Estado de Sao Paulo, Brazil