Glutamatergic receptors of the rostral ventrolateral medulla are involved in the ventilatory response to hypoxia

Paula, Patrícia Maria de; Branco, Luiz G.S.

doi:10.1016/j.resp.2004.11.012

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…Although injection of AP-5 and DNQX into the Bötz/C1 region failed to reduce the sympathetic component of the central chemoreflex, a previous study showed that these treatments abolished the increase in MAP and sSND produced by activation of peripheral chemoreceptors (10,41). Therefore, we tested the effects of the same doses of AP-5 and DNQX (100 mM in 50 nl) on the pressor and sSND responses to peripheral chemoreflex activation with intravenous NaCN.…”

Section: Resultsmentioning

confidence: 94%

Ventrolateral medulla mechanisms involved in cardiorespiratory responses to central chemoreceptor activation in rats

Takakura

Colombari

Menani

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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A rise in arterial Pco(2) stimulates breathing and sympathetic activity to the heart and blood vessels. In the present study, we investigated the involvement of the retrotrapezoid nucleus (RTN) and glutamatergic mechanisms in the Bötzinger/C1 region (Bötz/C1) in these responses. Splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) were recorded in urethane-anesthetized, sino-aortic-denervated, vagotomized, and artificially ventilated rats subjected to hypercapnia (end-expiratory CO(2) from 5% to 10%). Phrenic activity was absent at end-expiratory CO(2) of 4%, and strongly increased when end-expiratory CO(2) reached 10%. Hypercapnia also increased sSND by 103 ± 7%. Bilateral injections of the GABA-A agonist muscimol (2 mM) into the RTN eliminated the PND and blunted the sSND activation (Δ = +56 ± 8%) elicited by hypercapnia. Injections of NMDA receptor antagonist AP-5 (100 mM), non-NMDA receptor antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX; 100 mM) or metabotropic glutamate receptor antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG; 100 mM) bilaterally into the Bötz/C1 reduced PND (Δ = +43 ± 7%, +52 ± 6% or +56 ± 11%, respectively). MCPG also reduced sSND (Δ = +41 ± 7%), whereas AP-5 and DNQX had no effect. In conclusion, the increase in sSND caused by hypercapnia depends on increased activity of the RTN and on metabotropic receptors in the Bötz/C1, whereas PND depends on increased RTN activity and both ionotropic and metabotropic receptors in the Bötz/C1.

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Section: Resultsmentioning

confidence: 94%

Ventrolateral medulla mechanisms involved in cardiorespiratory responses to central chemoreceptor activation in rats

Takakura

Colombari

Menani

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Neurones in the ventral respiratory column and the RVLM are activated directly, and indirectly, by hypoxia. (Sun and Reis, 1994; De Paula and Branco, 2005; Alheid and McCrimmon, 2008). Orexin A microinjection into the RVLM enhanced the sympatho‐excitatory response to hypoxia while reducing tachycardiac and phrenic responses.…”

Section: Discussionmentioning

confidence: 99%

Orexin A in rat rostral ventrolateral medulla is pressor, sympatho‐excitatory, increases barosensitivity and attenuates the somato‐sympathetic reflex

Shahid

Rahman

Pilowsky

2012

British J Pharmacology

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BACKGROUND AND PURPOSE The rostral ventrolateral medulla (RVLM) maintains sympathetic nerve activity (SNA), and integrates adaptive reflexes. Orexin A‐immunoreactive neurones in the lateral hypothalamus project to the RVLM. Microinjection of orexin A into RVLM increases blood pressure and heart rate. However, the expression of orexin receptors, and effects of orexin A in the RVLM on splanchnic SNA (sSNA), respiration and adaptive reflexes are unknown. EXPERIMENTAL APPROACH The effect of orexin A on baseline cardio‐respiratory variables as well as the somato‐sympathetic, baroreceptor and chemoreceptor reflexes in RVLM were investigated in urethane‐anaesthetized, vagotomized and artificially ventilated male Sprague‐Dawley rats (n= 50). orexin A and its receptors were detected with fluorescence immunohistochemistry. KEY RESULTS Tyrosine hydroxylase‐immunoreactive neurones in the RVLM were frequently co‐localized with orexin 1 (OX1) and orexin 2 (OX2) receptors and closely apposed to orexin A‐immunoreactive terminals. Orexin A injected into the RVLM was pressor and sympatho‐excitatory. Peak effects were observed at 50 pmol with increased mean arterial pressure (42 mmHg) and SNA (45%). Responses to orexin A (50 pmol) were attenuated by the OX1 receptor antagonist, SB334867, and reproduced by the OX2 receptor agonist, [Ala11, D‐Leu15]orexin B. Orexin A attenuated the somato‐sympathetic reflex but increased baroreflex sensitivity. Orexin A increased or reduced sympatho‐excitation following hypoxia or hypercapnia respectively. CONCLUSIONS AND IMPLICATIONS Although central cardio‐respiratory control mechanisms at rest do not rely on orexin, responses to adaptive stimuli are dramatically affected by the functional state of orexin receptors.

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“…The concentrations of these drugs were selected based on previous reports (Ferreira et al . , de Paula & Branco ).…”

Section: Methodsmentioning

confidence: 99%

“…The ionotropic glutamate receptor antagonist, KY (10 nmol/0.1 lL; Sigma Chemical, St. Louis, MO, USA), and the metabotropic glutamate receptor antagonist, MCPG (10 nmol/0.1 lL; Sigma Chemical), were dissolved in pyrogen-free sterile saline. The concentrations of these drugs were selected based on previous reports (Ferreira et al 2004, de Paula & Branco 2005.…”

Section: Drugsmentioning

confidence: 99%

Ionotropic but not metabotropic glutamatergic receptors in the locus coeruleus modulate the hypercapnic ventilatory response in unanaesthetized rats

et al. 2013

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Glutamatergic receptors of the rostral ventrolateral medulla are involved in the ventilatory response to hypoxia

Cited by 10 publications

References 39 publications

Ventrolateral medulla mechanisms involved in cardiorespiratory responses to central chemoreceptor activation in rats

Ventrolateral medulla mechanisms involved in cardiorespiratory responses to central chemoreceptor activation in rats

Orexin A in rat rostral ventrolateral medulla is pressor, sympatho‐excitatory, increases barosensitivity and attenuates the somato‐sympathetic reflex

Ionotropic but not metabotropic glutamatergic receptors in the locus coeruleus modulate the hypercapnic ventilatory response in unanaesthetized rats

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