Involvement of L-glutamate and ATP in the neurotransmission of the sympathoexcitatory component of the chemoreflex in the commissural nucleus tractus solitarii of awake rats and in the working heart-brainstem preparation (original) (raw)
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NMDA receptors in NTS are involved in bradycardic but not in pressor response of chemoreflex
The American journal of physiology, 1995
Activation of carotid chemoreceptors with intravenous potassium cyanide (KCN) produces increases in arterial pressure, bradycardia, and tachypnea. In the present study, we activated carotid chemoreceptors with KCN and the neurotransmission of the chemoreceptor reflex into the commissural nucleus tractus solitarii (NTS) was blocked with phosphonovaleric acid (AP-5), an N-methyl-D-aspartate (NMDA)-selective antagonist. The aim of this study was to evaluate the involvement of NMDA receptors in the cardiovascular and respiratory responses produced by chemoreceptor activation in unanesthetized rats. The pressor response to KCN was not changed after microinjection of three different doses of AP-5 into the NTS, whereas the bradycardic response was reduced in a dose-dependent manner. The increase in respiratory frequency in response to carotid chemoreceptor activation was also not affected by AP-5 microinjected into the NTS. The data indicate that the activation of the cardiovagal component...
Sympathoexcitatory neurotransmission of the chemoreflex in the NTS of awake rats
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1999
Cardiovascular responses to chemoreflex activation by potassium cyanide (KCN, 20 μg/rat iv) were analyzed before and after the blockade of ionotropic or metabotropic receptors into the nucleus of the solitary tract (NTS) of awake rats. Microinjection of ionotropic antagonists [6,7-dinitroquinoxaline-2,3-dione or kynurenic acid (Kyn)] into the lateral commissural NTS (NTSlat), the midline commissural NTS (NTSmid), or into both (NTSlat+mid), produced a significant increase in basal mean arterial pressure, and the pressor response to chemoreflex activation was only partially reduced, whereas microinjection of Kyn into the NTSmid produced no changes in the pressor response to the chemoreflex. The bradycardic response to chemoreflex activation was abolished by microinjection of Kyn into the NTSlat or into NTSlat+mid but not by Kyn microinjection into the NTSmid. Microinjection of α-methyl-4-carboxyphenylglycine, a metabotropic receptor antagonist, into the NTSlat or NTSmid produced no ch...
Brazilian Journal of Medical and Biological Research, 2000
The neurotransmission of the chemoreflex in the nucleus tractus solitarii (NTS), particularly of the sympatho-excitatory component, is not completely understood. There is evidence that substance P may play a role in the neurotransmission of the chemoreflex in the NTS. Microinjection of substance P (50 pmol/50 nl, N = 12, and 5 nmol/50 nl, N = 8) into the commissural NTS of unanesthetized rats produced a significant increase in mean arterial pressure (101 ± 1 vs 108 ± 2 and 107 ± 3 vs 115 ± 4 mmHg, respectively) and no significant changes in heart rate (328 ± 11 vs 347 ± 15 and 332 ± 7 vs 349 ± 13 bpm, respectively) 2 min after microinjection. Previous treatment with WIN, an NK-1 receptor antagonist (2.5 nmol/50 nl), microinjected into the NTS of a specific group of rats, blocked the pressor (11 ± 5 vs 1 ± 2 mmHg) and tachycardic (31 ± 6 vs 4 ± 3 bpm) responses to substance P (50 pmol/50 nl, N = 5) observed 10 min after microinjection. Bilateral microinjection of WIN into the lateral commissural NTS (N = 8) had no significant effect on the pressor (50 ± 4 vs 42 ± 6 mmHg) or bradycardic (-230 ± 16 vs-220 ± 36 bpm) responses to chemoreflex activation with potassium cyanide (iv). These data indicate that the activation of NK-1 receptors by substance P in the NTS produces an increase in baseline mean arterial pressure and heart rate. However, the data obtained with WIN suggest that substance P and NK-1 receptors do not play a major role in the neurotransmission of the chemoreflex in the lateral commissural NTS.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2011
Presympathetic neurons in the different anteroposterior aspects of rostral ventrolateral medulla (RVLM) are colocalized with expiratory [Bötzinger complex (BötC)] and inspiratory [pre-Bötzinger complex (pre-BötC)] neurons of ventral respiratory column (VRC), suggesting that this region integrates the cardiovascular and respiratory chemoreflex responses. In the present study, we evaluated in different anteroposterior aspects of RVLM of awake rats the role of ionotropic glutamate and purinergic receptors on cardiorespiratory responses to chemoreflex activation. The bilateral ionotropic glutamate receptors antagonism with kynurenic acid (KYN) (8 nmol/50 nl) in the rostral aspect of RVLM (RVLM/BötC) enhanced the tachypneic (120 ± 9 vs. 180 ± 9 cpm; P < 0.01) and attenuated the pressor response (55 ± 2 vs. 15 ± 1 mmHg; P < 0.001) to chemoreflex activation ( n = 7). On the other hand, bilateral microinjection of KYN into the caudal aspect of RVLM (RVLM/pre-BötC) caused a respiratory...
2011
In the present study, we evaluated the role of glutamatergic mechanisms in the retrotrapezoid nucleus (RTN) in changes of splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) elicited by central and peripheral chemoreceptor activation. Mean arterial pressure (MAP), sSND and PND were recorded in urethane-anaesthetized, vagotomized, sino-aortic denervated and artificially ventilated male Wistar rats. Hypercapnia (10% CO 2 ) increased MAP by 32 ± 4 mmHg, sSND by 104 ± 4% and PND amplitude by 101 ± 5%. Responses to hypercapnia were reduced after bilateral injection of the NMDA receptor antagonist d,l-2-amino-5-phosphonovalerate (AP-5; 100 mm in 50 nl) in the RTN (MAP increased by 16 ± 3 mmHg, sSND by 82 ± 3% and PND amplitude by 63 ± 7%). Bilateral injection of the non-NMDA receptor antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX; 100 mm in 50 nl) and the metabotropic receptor antagonist (+/−)-α-methyl-4-carboxyphenylglycine (MCPG; 100 mm in 50 nl) in the RTN did not affect sympathoexcitatory responses induced by hypercapnia. Injection of DNQX reduced hypercapnia-induced phrenic activation, whereas MCPG did not. In animals with intact carotid chemoreceptors, bilateral injections of AP-5 and DNQX in the RTN reduced increases in MAP, sSND and PND amplitude produced by intravenous injection of NaCN (50 μg kg −1 ). Injection of MCPG in the RTN did not change responses produced by NaCN. These data indicate that RTN ionotropic glutamatergic receptors are involved in the sympathetic and respiratory responses produced by central and peripheral chemoreceptor activation.
Autonomic processing of the cardiovascular reflexes in the nucleus tractus solitarii
Brazilian Journal of Medical and Biological Research, 1997
The nucleus tractus solitarii (NTS) receives afferent projections from the arterial baroreceptors, carotid chemoreceptors and cardiopulmonary receptors and as a function of this information produces autonomic adjustments in order to maintain arterial blood pressure within a narrow range of variation. The activation of each of these cardiovascular afferents produces a specific autonomic response by the excitation of neuronal projections from the NTS to the ventrolateral areas of the medulla (nucleus ambiguus, caudal and rostral ventrolateral medulla). The neurotransmitters at the NTS level as well as the excitatory amino acid (EAA) receptors involved in the processing of the autonomic responses in the NTS, although extensively studied, remain to be completely elucidated. In the present review we discuss the role of the EAA L-glutamate and its different receptor subtypes in the processing of the cardiovascular reflexes in the NTS. The data presented in this review related to the neurotransmission in the NTS are based on experimental evidence obtained in our laboratory in unanesthetized rats. The two major conclusions of the present review are that a) the excitation of the cardiovagal component by cardiovascular reflex activation (chemo-and Bezold-Jarisch reflexes) or by L-glutamate microinjection into the NTS is mediated by N-methyl-D-aspartate (NMDA) receptors, and b) the sympatho-excitatory component of the chemoreflex and the pressor response to L-glutamate microinjected into the NTS are not affected by an NMDA receptor antagonist, suggesting that the sympatho-excitatory component of these responses is mediated by non-NMDA receptors.
Cardiorespiratory responses to glutamatergic antagonists in the caudal ventrolateral medulla of rats
Brain Research, 1991
The role of caudal ventrolateral medullary (CVLM) depressor neurons in influencing arterial pressure and ventilation as well as the baroreflex control of arterial pressure was investigated, and the part played by excitatory N-methyl-D-aspartate (NMDA) and non-NMDA receptors in mediating the responses was determined. In urethane-anesthetized, spontaneously breathing rats unilateral microinjections into the caudal depressor area of the broad-band glutamatergic antagonist kynurenic acid (KYN, 5 nmol or 1.58 nmol), or NMDA antagonist 2-amino-5-phosphonovaleric acid (2-APV, 2.7 nmol), or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 0.257 nmol) caused a respiratory arrest within 4 min and the animals had to be artificially ventilated. Respiratory frequency increased on injecting KYN and CNQX while it did not change significantly with 2-APV. Apnea resulted from progressive decrease in tidal volume. During the apnea ventilation with 5% CO2 did not revive breathing. Mean arterial pressure (MAP) increased significantly with KYN and 2-APV injections but not with CNQX. The baroreflex decrease of MAP, elicited by left or right aortic depressor nerve stimulation, was significantly reduced or abolished after bilateral microinjections of all 3 antagonists. Ventilation as well as the baroreflex usually recovered after 1-1.5 h. Microinjections of the same doses of antagonists into the facial nucleus, as well as application of KYN (25 nmol) to the ventral medullary surface above the hypoglossal rootlets, had no significant effect. The results support previous findings that the CVLM neurons of the rat inhibit sympathetic neurons providing the vasomotor tone, and that an intact CVLM is obligatory for mediating the baroreflex decrease of arterial pressure. The results also indicate that: (1) the CVLM is essential for sustaining ventilation in the rat; (2) only NMDA receptors are involved in maintaining baseline blood pressure while both NMDA and non-NMDA receptors mediate the baroreceptor depressor reflex; and (3) both NMDA and non-NMDA receptor activation is necessary to sustain ventilation.
Autonomic Neuroscience, 2002
Activation of the chemoreflex with potassium cyanide (KCN, 40 Ag/rat, i.v.) in awake rats produces pressor and bradycardic responses as well as a tachypneic response. In the present study, we evaluated the involvement of the periaqueductal gray matter (PAG) and the parabrachial nucleus (PBN) in the neural pathways of the cardiovascular responses to chemoreflex activation. The cardiovascular responses to chemoreflex activation were evaluated before and after bilateral microinjection of 2% lidocaine, a local anesthetic, into the PBN or PAG in order to block in a reversible manner the neuronal activity and axonal conduction of fibers of passage in these areas. The data show that the pressor response to chemoreflex activation 3 min after bilateral microinjection of lidocaine into the dorsolateral aspect of the PBN was significantly reduced in comparison to the control response (32 F 5 vs. 48 F 4 mm Hg, n = 7), with no significant changes in the bradycardic responses. The effect of lidocaine was reversible since the pressor response was back to control levels 15 min after microinjection of this anesthetic. Bilateral microinjections of lidocaine into the dorsolateral (n = 11) or lateral (n = 8) columns of the PAG in distinct groups of rats produced no significant changes in the pressor or bradycardic responses of the chemoreflex. These data indicate that the PBN is part of the neuronal pathways involved in the sympathoexcitatory component of the chemoreflex while the PAG is not. D
Naunyn-Schmiedeberg's Archives of Pharmacology, 2007
Cholecystokinin (CCK) elicits a sympathetic vasomotor reflex that is implicated in gastrointestinal circulatory control. We sought to determine (1) the site in the solitary tract nucleus (NTS) responsible for mediating this reflex and (2) the possible involvement of excitatory amino acid (EAA) receptors. In addition, we sought to determine whether the NTS site responsible for mediating the baroreflex (phenylephrine, PE, 10 µg/kg i.v.) and the von Bezold-Jarisch reflex (phenylbiguanide, PBG, 10 µg/kg i.v) overlap with that involved in the CCK-induced reflex (CCK, 4 µg/kg, i.v.), and to compare the relative importance of NMDA and non-NDMA receptors in these reflexes. In separate experiments, the effects of PE, PBG, and CCK on mean arterial blood pressure, heart rate, and splanchnic sympathetic nerve discharge were tested before and after bilateral microinjection into the NTS of the γ-aminobutyric acid A (GABA A) agonist muscimol, the EAA antagonist kynurenate, the NMDA receptor antagonist D(−)-2-amino-5phosphopentanoic acid (AP-5), the non-NMDA receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), AP-5+NBQX, or vehicle. While all treatments (except vehicle) significantly attenuated/ abolished/reversed the splanchnic sympathoinhibitory responses to PE, PBG, and CCK, the extent of blockade varied between the different treatment groups. Both NMDA and non-NMDA receptors were essential to the baroreflex and the von Bezold-Jarisch reflex, whereas the CCK reflex was more dependent on non-NMDA receptors. Muscimol, kynurenate, and AP-5+NBQX significantly attenuated the bradycardic responses to PE and PBG (P<0.05), whereas AP-5, NBQX, or vehicle did not. The bradycardic responses to CCK remained intact after all treatments. These results suggest that while there is overlap in the area of the NTS responsible for eliciting all three reflexes, NMDA and non-NMDA receptors are recruited differentially for the full expression of these reflexes. The CCK-induced sympathoinhibitory reflex is unique in that it relies predominantly on non-NMDA receptors in the NTS and elicits bradycardic effects that are independent of the NTS.