João H Costa-Silva

University of São Paulo, São Paulo, Estado de Sao Paulo, Brazil

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Publications (4)6.59 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: 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 activity. Using arterially-perfused in situ preparations, we observed that SH rats (n=20), but not controls, exhibited late-expiratory (late-E) bursts in abdominal nerve (P<0.05) associated with depressed post-inspiratory and increased augmenting-expiratory activities of neurons in the Bötzinger complex (BötC, P<0.05). SH rats also exhibited additional late-E bursts in thoracic sympathetic activity associated with larger Traube-Hering wave amplitudes (P<0.05). Corroborating these findings, we observed in unanesthetized rats that the arterial pressure levels of SH rats (n=7) exhibited augmented low-and high-frequency variabilities (P<0.05). Besides, the antagonism of ionotropic glutamate receptors in the BötC eliminated the late-E activity in respiratory and sympathetic nerves. Our data indicate that short-term SH alters the expiratory pattern and its coupling with sympathetic nervous system by mechanisms involving changes of neuronal activities and glutamatergic transmission in the BötC.
    Experimental Biology; 04/2013
  • João H Costa-Silva, Daniel B Zoccal, Benedito H Machado
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    ABSTRACT: Sympathetic overactivity and altered respiratory control are commonly observed after chronic intermittent hypoxia (CIH) exposure. However, the central mechanisms underlying such neurovegetative dysfunctions remain unclear. Herein, we hypothesized that CIH (6% O(2) every 9 min, 8 h/day, 10 days) in juvenile rats alters glutamatergic transmission in the commissural nucleus tractus solitarius (cNTS), a pivotal site for integration of peripheral chemoreceptor inputs. Using an in situ working heart-brain stem preparation, we found that l-glutamate microinjections (1, 3, and 10 mM) into the cNTS of control rats (n = 8) evoked increases in thoracic sympathetic nerve (tSN) and central vagus nerve (cVN) activities combined with inhibition of phrenic nerve (PN) activity. Besides, the ionotropic glutamatergic receptor antagonism with kynurenic acid (KYN; 250 mM) in the cNTS of control group (n = 7) increased PN burst duration and frequency. In the CIH group (n = 10), the magnitude of l-glutamate-induced cVN excitation was smaller, and the PN inhibitory response was blunted (P < 0.05). In addition, KYN microinjections into the cNTS of CIH rats (n = 9) did not alter PN burst duration and produced smaller increases in its frequency compared with controls. Moreover, KYN microinjections into the cNTS attenuated the sympathoexcitatory response to peripheral chemoreflex activation in control but not in CIH rats (P < 0.05). These functional CIH-induced alterations were accompanied by a significant 10% increase of N-methyl-D-aspartate receptor 1 (NMDAR1) and glutamate receptor 2/3 (GluR2/3) receptor subunit density in the cNTS (n = 3-8, P < 0.05), evaluated by Western blot analysis. These data indicate that glutamatergic transmission is altered in the cNTS of CIH rats and may contribute to the sympathetic and respiratory changes observed in this experimental model.
    AJP Regulatory Integrative and Comparative Physiology 12/2011; 302(6):R785-93. · 3.28 Impact Factor
  • Autonomic Neuroscience-basic & Clinical - AUTON NEUROSCI-BASIC CLIN. 01/2011; 163(1):116-117.
  • João H Costa-Silva, Daniel B Zoccal, Benedito H Machado
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    ABSTRACT: For a better understanding of the processing at the nucleus tractus solitarius (NTS) level of the autonomic and respiratory responses to peripheral chemoreceptor activation, herein we evaluated the role of glutamatergic neurotransmission in the intermediate (iNTS) and caudal NTS (cNTS) on baseline respiratory parameters and on chemoreflex-evoked responses using the in situ working heart-brain stem preparation (WHBP). The activities of phrenic (PND), cervical vagus (cVNA), and thoracic sympathetic (tSNA) nerves were recorded before and after bilateral microinjections of kynurenic acid (Kyn, 5 nmol/20 nl) into iNTS, cNTS, or both simultaneously. In WHBP, baseline sympathetic discharge markedly correlated with phrenic bursts (inspiration). However, most of sympathoexcitation elicited by chemoreflex activation occurred during expiration. Kyn microinjected into iNTS or into cNTS decreased the postinspiratory component of cVNA and increased the duration and frequency of PND. Kyn into iNTS produced no changes in sympathoexcitatory and tachypneic responses to peripheral chemoreflex activation, whereas into cNTS, a reduction of the sympathoexcitation, but not of the tachypnea, was observed. The pattern of phrenic and sympathetic coupling during the chemoreflex activation was an inspiratory-related rather than an expiratory-related sympathoexcitation. Kyn simultaneously into iNTS and cNTS produced a greater decrease in postinspiratory component of cVNA and increase in frequency and duration of PND and abolished the respiratory and autonomic responses to chemoreflex activation. The data show that glutamatergic neurotransmission in the iNTS and cNTS plays a tonic role on the baseline respiratory rhythm, contributes to the postinspiratory activity, and is essential to expiratory-related sympathoexcitation observed during chemoreflex activation.
    Journal of Neurophysiology 02/2010; 103(4):2095-106. · 3.30 Impact Factor