Involvement of the purinergic system in central cardiovascular modulation at the level of the nucleus ambiguus of anaesthetized rats

Passamani, Luciana Mesquita; Pedrosa, Diego França; Mauad, Helder; Schenberg, Luiz Carlos; Paton, Julian F. R.; Sampaio, Karla Nívea

doi:10.1113/expphysiol.2010.054882

Cited by 9 publications

(7 citation statements)

References 38 publications

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“…Importantly, ATP has been shown to act as a cotransmitter with glutamate (Braga et al 2007;Pankratov et al 1998Pankratov et al , 2002Passamani et al 2011;Scislo and O'Leary 2000), and we recently showed that ATP-evoked sympathoexcitatory responses within the PVN were blunted in the presence of ionotropic glutamate receptor blockade (Ferreira-Neto et al 2013). Similar to this previous study, we found here that the ionotropic glutamatergic receptor antagonist KYN abolished the ATP-evoked increase in firing activity in PVN sympathetic neurons.…”

Section: Discussionsupporting

confidence: 80%

ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents

Ferreira‐Neto

Antunes

Stern

2015

Journal of Neurophysiology

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Ferreira-Neto HC, Antunes VR, Stern JE. ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptormediated currents. J Neurophysiol 114: 159 -169, 2015. First published April 22, 2015 doi:10.1152/jn.01011.2014.-We have previously shown that ATP within the paraventricular nucleus (PVN) induces an increase in sympathetic activity, an effect attenuated by the antagonism of P2 and/or glutamatergic receptors. Here, we evaluated precise cellular mechanisms underlying the ATP-glutamate interaction in the PVN and assessed whether this receptor coupling contributed to osmotically driven sympathetic PVN neuronal activity. Whole-cell patch-clamp recordings obtained from PVN-rostral ventrolateral medulla neurons showed that ATP (100 M, 1 min, bath applied) induced an increase in firing rate (89%), an effect blocked by kynurenic acid (1 mM) or 4-[[4-Formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3-benzenedisulfonic acid tetrasodium salt (PPADS) (10 M). Whereas ATP did not affect glutamate synaptic function, ␣-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor-mediated currents evoked by focal application of AMPA (50 M, n ϭ 13) were increased in magnitude by ATP (AMPA amplitude: 33%, AMPA area: 52%). ATP potentiation of AMPA currents was blocked by PPADS (n ϭ 12) and by chelation of intracellular Ca 2ϩ (BAPTA, n ϭ 10). Finally, a hyperosmotic stimulus (mannitol 1%, ϩ55 mosM, n ϭ 8) potentiated evoked AMPA currents (53%), an effect blocked by PPADS (n ϭ 6). Taken together, our data support a functional stimulatory coupling between P2 and AMPA receptors (likely of extrasynaptic location) in PVN sympathetic neurons, which is engaged in response to an acute hyperosmotic stimulus, which might contribute in turn to osmotically driven sympathoexcitatory responses by the PVN.ATP; ␣-amino-3-hydroxy-5-methylisoxazole propionic acid; paraventricular nucleus; rostral ventrolateral medulla; hyperosmolarity BODY FLUID HOMEOSTASIS is tightly regulated by the integration of renal, cardiovascular, and neuroendocrine systems (Share and Claybaugh 1972). An increase in plasma osmolality induces several responses including an increase in sympathetic activity, blood pressure elevation, and the release of neurohormones, such as vasopressin and angiotensin II (Bealer 2000;Hatzinikolaou et al. 1980Hatzinikolaou et al. , 1981Stocker and Toney 2005;Weiss et al. 1996). Part of these responses are mediated through activation of the hypothalamic paraventricular nucleus (PVN) driven by the circumventricular organs in which central osmoreceptors are located (Antunes-Rodrigues et al. 2004;Stocker et al. 2008). The PVN is composed of magnocellular and parvocellular neurons. Magnocellular neurons synthesize and release vasopressin and oxytocin systemically from the posterior pituitary, whereas parvocellular neurons project to premotor sympathoexcitatory neurons located either in the rostral ventrolateral medulla (RVLM) and/or intermediolateral cell column of the spinal cord.Several neurotransmitters in t...

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Section: Discussionsupporting

confidence: 80%

ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents

Ferreira‐Neto

Antunes

Stern

2015

Journal of Neurophysiology

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“…The suggestion that CVMs from the dorsal motor vagal nucleus might be selectively activated by cardiopulmonary inputs (Daly and Kirkman, 1989; Jones and Daly, 1997) no longer appears tenable (Jones, 2001; Wang et al, 2000). The bradycardia evoked by stimulation of cardiopulmonary afferents in the rat is attenuated after bilateral microinjection of P2X antagonist in the nucleus ambiguus suggesting CVMs in this region are also activated by this input via release of purines (Passamani et al, 2011). Interestingly, an essential role for CVMs in the dorsal motor vagal nucleus has recently been proposed for the cardioprotective effects of remote ischemic preconditioning in this species (Mastitskaya et al, 2012) which appears to be independent of effects on heart rate.…”

Section: Discussionmentioning

confidence: 99%

Chronotropic and dromotropic responses to localized glutamate microinjections in the rat nucleus ambiguus

et al. 2014

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The cardioinhibitory effects of cardiac vagal motoneurons (CVMs) are mediated by activation of postganglionic neurons in the epicardial ganglia which have been shown to exert functionally selective effects on heart rate and atrioventricular conduction in the rat. Here we investigate whether CVMs producing these responses may occupy different rostrocaudal positions within the nucleus ambiguus. Excitation of CVMs was attempted by microinjections of glutamate into the nucleus ambiguus of an arterially perfused preparation in a grid extending over 2 mm in the rostrocaudal plane using the obex as a reference point. Microinjections were paired, one made during pacing to measure changes in atrioventricular conduction (P-R interval) independent of changes in heart rate and the other looking for changes in heart period (P-P interval) un-paced. Although evidence of a differential distribution was found in 7 cases, in the majority (13/20), sites producing maximal effects on both variables coincided. Maximal changes in atrioventricular conduction resulted from more rostral sites in 6 cases and from a more caudal site in only one. Overall, the ratio of the change in atrioventricular conduction to the change in heart rate for a given site was significantly greater 1 mm rostral to the obex than at either end of the test grid. We conclude that while CVMs controlling atrioventricular conduction are distributed with a peak somewhat rostral to those controlling heart rate in a number of animals, there is a significant overlap and much greater variability in this distribution in the rat than in cats and dogs.

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“…In the RVLM, Ralevic et al [53] and Horiuchi et al [54] have shown that there does not appear to be an interplay between purinergic and glutamatergic systems. However, in other brain nuclei, several studies have demonstrated that ATP and glutamate can function as cotransmitters [39,41,[55][56][57]. For example, in nucleus of the solitary tract (NTS) neurons, the fast responses to stimulation of P2X receptors are mediated via glutamatergic ionotropic mechanisms [58].…”

Section: Discussionmentioning

confidence: 99%

Purinergic and glutamatergic interactions in the hypothalamic paraventricular nucleus modulate sympathetic outflow

Ferreira‐Neto

Yao

Antunes

2013

Purinergic Signalling

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P2X receptors are expressed on ventrolateral medulla projecting paraventricular nucleus (PVN) neurons. Here, we investigate the role of adenosine 5′-triphosphate (ATP) in modulating sympathetic nerve activity (SNA) at the level of the PVN. We used an in situ arterially perfused rat preparation to determine the effect of P2 receptor activation and the putative interaction between purinergic and glutamatergic neurotransmitter systems within the PVN on lumbar SNA (LSNA). Unilateral microinjection of ATP into the PVN induced a dose-related increase in the LSNA (1 nmol: 38±6 %, 2.5 nmol: 72±7 %, 5 nmol: 96± 13 %). This increase was significantly attenuated by blockade of P2 receptors (pyridoxalphosphate-6-azophenyl-20,40-disulphonic acid, PPADS) and glutamate receptors (kynurenic acid, KYN) or a combination of both. The increase in LSNA elicited by L-glutamate microinjection into the PVN was not affected by a previous injection of PPADS. Selective blockade of non-Nmethyl-D-aspartate receptors (6-cyano-7-nitroquinoxaline-2,3-dione disodium salt, CNQX), but not N-methyl-D-aspartate receptors (NMDA) receptors (DL-2-amino-5-phosphonopentanoic acid, AP5), attenuated the ATP-induced sympathoexcitatory effects at the PVN level. Taken together, our data show that purinergic neurotransmission within the PVN is involved in the control of SNA via P2 receptor activation. Moreover, we show an interaction between P2 receptors and non-NMDA glutamate receptors in the PVN suggesting that these functional interactions might be important in the regulation of sympathetic outflow.

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Involvement of the purinergic system in central cardiovascular modulation at the level of the nucleus ambiguus of anaesthetized rats

Cited by 9 publications

References 38 publications

ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents

ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents

Chronotropic and dromotropic responses to localized glutamate microinjections in the rat nucleus ambiguus

Purinergic and glutamatergic interactions in the hypothalamic paraventricular nucleus modulate sympathetic outflow

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