Modulation of arterial baroreflexes by antisense oligodeoxynucleotides to NMDAR1 receptors in the nucleus tractus solitarius

Dean, Caron; Hermes, Catchia; Robinson, John K.; Seagard, J. L.

doi:10.1016/s0165-1838(98)00147-7

Cited by 11 publications

(4 citation statements)

References 33 publications

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“…Previous studies showed that prior microinjection of a subthreshold dose of DOI into the NTS enhances the bradycardia elicited either by aortic and/or carotid baroreceptor activation, or by local N ‐methyl‐ d ‐aspartate (NMDA) receptor stimulation (N'Diaye et al ., 2001), the latter playing a key role in baroreflex signalling at the level of the NTS (Dean et al ., 1998). We here noted that the baroreflex bradycardia induced by either aortic occlusion or aortic nerve stimulation, as well as the cardiac baroreflex gain observed after graded aortic constriction, were potentiated by a noneffective dose of DOI, confirming the facilitatory influence of NTS 5‐HT 2A receptor stimulation on the aortic cardiac response.…”

Section: Discussionsupporting

confidence: 68%

Activation of nucleus tractus solitarius 5‐HT_2Abut not other 5‐HT₂receptor subtypes inhibits the sympathetic activity in rats

Comet¹,

Bernard²,

Hamon³

et al. 2007

Eur J of Neuroscience

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Our first aim was to elucidate the mechanisms underlying the hypotensive response elicited by 5-HT(2) receptor activation in the nucleus tractus solitarius (NTS). In pentobarbitone-anaesthetized rats, intra-NTS administration of 2,5-dimethoxy-4-iodoamphetamine (DOI), a wide spectrum 5-HT(2) receptor agonist, but not an antagonist of selective 5-HT(2B) and 5-HT(2C) receptors, produced a decrease in blood pressure and heart rate. The maximal cardiovascular changes obtained by DOI (0.5 pmol) could be almost completely abolished by prior intra-NTS microinjection (10 pmol) of MDL-100907, a selective 5-HT(2A) receptor antagonist, but not by 5-HT(2B) or 5-HT(2C) receptor antagonists. In addition, using extracellular recordings we found that the large majority of identified cardiovascular rostroventrolateral medulla (RVLM) neurons were almost totally inhibited by NTS 5-HT(2A) receptor stimulation. We then investigated whether intra-NTS administration of a subthreshold dose (0.05 pmol) of DOI, known to facilitate the cardiovagal component of the baroreflex, could also modulate the sympathoinhibitory component of this reflex. These experiments showed that neither the decrease in the activity of the cardiovascular RVLM neurons and lumbar sympathetic nerve activities produced by aortic occlusion (gain of the baroreflex), nor the hypotensive response elicited by aortic nerve stimulation, were potentiated by the microinjection of DOI under such conditions. These data show that activation of 5-HT(2A), but not 5-HT(2B) or 5-HT(2C), receptors, located on NTS neurons, elicits depressor and bradycardic responses, and that this 5-HT(2A)-mediated hypotension is produced via the inhibition of RVLM cardiovascular neurons. In addition, NTS 5-HT(2A) receptor activation facilitates the cardiac but not the sympathetic baroreflex response.

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Section: Discussionsupporting

confidence: 68%

Activation of nucleus tractus solitarius 5‐HT_2Abut not other 5‐HT₂receptor subtypes inhibits the sympathetic activity in rats

Comet¹,

Bernard²,

Hamon³

et al. 2007

Eur J of Neuroscience

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“…NMDA, AMPA, and KA receptors play a differential role in synaptic response of NTS neurons to activation of afferent fibers (Kubo and Kihara, 1991;Dingledine et al, 1999;Yen et al, 1999). Blockade of NR1 mRNA in the NTS with an antisense oligonucleotide attenuates BRR sensitivity (Dean et al, 1998). Superimposed on this information, the present study demonstrated that NR1, NR2A, GluR1, GluR4, or KA1 subunit undergoes an augmentation in molecular synthesis after brief hyperthermic HS and contributes functionally to the potentiation of glutamatergic neurotransmission in the NTS by HSP70 seen after HS.…”

Section: Up-regulation Of Glutamate Receptors By Heat Shock Protein 1101mentioning

confidence: 99%

Up-Regulation of Glutamate Receptors in Nucleus Tractus Solitarii Underlies Potentiation of Baroreceptor Reflex by Heat Shock Protein 70

Chan

Chang²,

Ou³

et al. 2002

Mol Pharmacol

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Whereas induction of the 70-kDa heat shock protein (HSP70) in the nucleus tractus solitarii (NTS), the terminal site in the brain stem for primary baroreceptor afferents, augments baroreceptor reflex (BRR) response, the underlying cellular and molecular mechanism is essentially unexplored. In Sprague-Dawley rats, we evaluated the hypothesis that HSP70 may potentiate BRR response by up-regulating the molecular synthesis and functional expression of glutamate receptors in the NTS. Animals subjected to brief hyperthermic heat shock (HS; 42°C for 15 min) exhibited augmented expression of NR1 or NR2A subunit of N-methyl-D-aspartate (NMDA) receptors, GluR1 or GluR4 subunits of ␣-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors and KA1 subunit of kainate receptors in the NTS. Intriguingly, this up-regulation of glutamate receptors was preceded by an increase in HSP70 expression at the NTS. The HS-induced augmentation in responsiveness of barosensitive NTS neurons to transient hypertension or potentiation of BRR response was discernibly blunted by MK-801 or 6-cyano-7-nitroquinoxaline-2,3-dione. Bilateral microinjection into the NTS of an antisense hsp70 oligonucleotide (50 pmol) before HS significantly suppressed the induced expression of HSP70 or the increase in glutamate receptor subunits in the dorsal medulla and discernibly attenuated the potentiation of BRR response. Control microinjection into the NTS of sense or scrambled hsp70 oligonucleotide (50 pmol) was ineffective. These findings suggest that HSP70 induced by HS may enhance BRR response by up-regulating the molecular synthesis and functional expression of NR1 or NR2A subunit of NMDA receptors and GluR1, GluR4, or KA1 subunit of non-NMDA receptors in the NTS.

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“…However, to date, the type of glutamate ionotropic receptor involved in the transmission of the cardiovascular messages in the NTS is still a matter of debate. Some authors propose that NTS NMDA receptors play a pivotal role in the transmission of these messages [25,39,67,96], while others suggest either the implication of both NTS NMDA and non-NMDA receptors [117,147,211,223] or that non-NMDA receptors exert a predominant role [63] in this process.…”

Section: Excitatory Amino Acidsmentioning

confidence: 99%

The Key Role of Medullary 5-HT3 Receptors in the Serotonin-Mediated Neural Control of Cardiovascular Function

Sévoz‐Couche¹,

Machado²,

Hamon³

et al. 2005

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The baroreceptor reflex plays a crucial role in the homeostatic control of cardiovascular parameters. In the central nervous system, the nucleus of the tractus solitarius (NTS) is critically involved in cardiovascular reflex control because it is both the first site of termination of glutamatergic baroreceptor afferent fibres and an important integrative area for the sensory afferent signals reaching the brainstem. In addition to glutamate, the NTS contains numerous neurotransmitters that could participate in the modulations of the baroreceptor reflex sensitivity which occur under various physiological conditions. In particular, a large body of evidence indicates that serotonin plays a modulatory role in the central control of blood pressure, especially at the level of the NTS, which is innervated by both central and peripheral serotonergic fibres. Indeed, serotonin exerts multiple cardiovascular influences through the activation of several receptors in the NTS. Actually, the NTS is the central area endowed with the highest density of serotonin 3 (5-HT 3 ) receptors whose stimulation triggers all the adaptive cardiovascular changes normally associated with behavioural responses to various stressful conditions.In this review, we first assess the current knowledge about the mechanisms underlying the cardiovascular effects of the specific activation of serotonergic receptors in the NTS. Secondly, we describe evidence that, in the NTS, 5-HT 3 receptors play a key role in one of the crucial homeostatic responses that characterise the defence reaction: the inhibitory modulation of the parasympathetic cardiac component of the baroreceptor reflex. The possible functional interactions of 5-HT 3 receptors with GABA A , NK 1 and NMDA receptors within the NTS are also discussed.

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Modulation of arterial baroreflexes by antisense oligodeoxynucleotides to NMDAR1 receptors in the nucleus tractus solitarius

Cited by 11 publications

References 33 publications

Activation of nucleus tractus solitarius 5‐HT_2Abut not other 5‐HT₂receptor subtypes inhibits the sympathetic activity in rats

Activation of nucleus tractus solitarius 5‐HT_2Abut not other 5‐HT₂receptor subtypes inhibits the sympathetic activity in rats

Up-Regulation of Glutamate Receptors in Nucleus Tractus Solitarii Underlies Potentiation of Baroreceptor Reflex by Heat Shock Protein 70

The Key Role of Medullary 5-HT3 Receptors in the Serotonin-Mediated Neural Control of Cardiovascular Function

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Modulation of arterial baroreflexes by antisense oligodeoxynucleotides to NMDAR1 receptors in the nucleus tractus solitarius

Cited by 11 publications

References 33 publications

Activation of nucleus tractus solitarius 5‐HT2Abut not other 5‐HT2receptor subtypes inhibits the sympathetic activity in rats

Activation of nucleus tractus solitarius 5‐HT2Abut not other 5‐HT2receptor subtypes inhibits the sympathetic activity in rats

Up-Regulation of Glutamate Receptors in Nucleus Tractus Solitarii Underlies Potentiation of Baroreceptor Reflex by Heat Shock Protein 70

The Key Role of Medullary 5-HT3 Receptors in the Serotonin-Mediated Neural Control of Cardiovascular Function

Contact Info

Product

Resources

About

Activation of nucleus tractus solitarius 5‐HT_2Abut not other 5‐HT₂receptor subtypes inhibits the sympathetic activity in rats

Activation of nucleus tractus solitarius 5‐HT_2Abut not other 5‐HT₂receptor subtypes inhibits the sympathetic activity in rats