No abstract

We investigated the role of glutamatergic projection from the parabrachial nucleus (PBN) complex to the rostral ventrolateral medulla (RVLM) in the PBN-induced suppression of reflex bradycardia in adult Sprague-Dawley rats that were maintained under pentobarbital anesthesia. Under stimulus conditions that did not appreciably alter the baseline systemic arterial pressure and heart rate, electrical (10-s train of 0.5-ms pulses, at 10–20 μA and 10–20 Hz) or chemical (l-glutamate, 1 nmol) stimulation of the ventrolateral regions and Köelliker-Fuse (KF) subnucleus of the PBN complex significantly suppressed the reflex bradycardia in response to transient hypertension evoked by phenylephrine (5 μg/kg iv). The PBN-induced suppression of reflex bradycardia was appreciably reversed by bilateral microinjection into the RVLM of the N-methyl-d-aspartate (NMDA)-receptor antagonist MK-801 (500 pmol) or the non-NMDA-receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (50 pmol). Anatomically, most of the retrogradely labeled neurons in the ventrolateral regions and KF subnucleus of the ipsilateral PBN complex after microinjection of fast blue into the RVLM were also immunoreactive to anti-glutamate antiserum. These results suggest that a direct glutamatergic projection to the RVLM from topographically distinct regions of the PBN complex may participate in the suppression of reflex bradycardia via activation of both NMDA and non-NMDA receptors at the RVLM.

No abstract

The involvement of glutamatergic neurotransmission in the rostral ventrolateral medulla (RVLM) in the suppression of baroreflex bradycardia by the parabrachial nucleus (PBN) was investigated. Repeated electrical activation of the PBN increased the concentration of glutamate in the dialysate collected from the RVLM. The same stimulation also suppressed baroreflex bradycardia in response to transient hypertension evoked by phenylephrine (5 microg/kg, intravenously). Microinfusion of L-glutamate (10, 50 or 100 microM) via the microdialysis probe into the RVLM dose-dependently elicited a significant inhibition of baroreflex bradycardia that paralleled the concentration and time course of the PBN-elicited elevation in extracellular glutamate in the RVLM. The suppression of baroreflex bradycardia elicited by microinjection of L-glutamate (1 nmol) into the RVLM was appreciably reversed by coinjection of the NMDA receptor antagonist, dizocilpine (500 pmol), or the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2, 3-dione (50 pmol). These results suggest that an increase in the extracellular concentration of glutamate and activation of both NMDA and non-NMDA receptors in the RVLM may mediate the suppression of baroreflex bradycardia by activation of the PBN.

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We investigated the role of GABAergic neurotransmission at the nucleus tractus solitarii (NTS) in the suppression of cardiac baroreceptor reflex (BRR) response induced by parabrachial nucleus (PBN) complex in adult Sprague-Dawley rats maintained under pentobarbital anesthesia. Based on in vivo microdialysis coupled with high-performance liquid chromatography-fluorescence detection for gamma-aminobutyric acid (GABA), we found that electrical stimulation of the ventrolateral regions and Koelliker-Fuse (KF) subnucleus of PBN complex resulted in a site-specific increase in GABA concentration in the dialysate collected from the NTS. The temporal increase in extracellular GABA concentration in the NTS coincided with the time course of PBN-induced cardiac BRR inhibition. In addition, the PBN-induced cardiac BRR suppression was reversed by microinjection bilaterally into the NTS of a GABA(A) receptor antagonist, bicuculline methiodide (5 pmol), or a GABA(B) receptor antagonist, 2-OH saclofen (500 pmol). Blockade of neuronal activity in the ventrolateral regions and KF subnucleus of PBN complex with lidocaine (5%) elicited an enhancement of the same reflex response. The time course of this facilitatory effect of lidocaine correlated positively with the temporal decrease in extracellular GABA concentration in the NTS. Anatomically, Fast Blue-labeled neurons were identified in the same subnuclei of the PBN complex after microinjection of the retrograde transport tracer into the NTS. Some of these Fast Blue-labeled neurons were also immunoreactive to glutamic acid decarboxylase. These results suggest that a direct GABAergic descending projection from the KF subnucleus and surrounding areas of the PBN complex to the NTS may inhibit cardiac BRR response by activating GABA(A) and GABA(B) receptors at the NTS.

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We applied reverse microdialysis and HPLC analysis to evaluate the participation of noradrenergic neurotransmission in modulation of the baroreceptor reflex response by substance P at the nucleus tractus solitarii in Sprague‐Dawley rats anesthetized with pentobarbital sodium (50 mg/kg, i.p., with 20 mg/kg/h.i.v. supplement). Continuous infusion of substance P (600 µM) at 1 µl/min into the nucleus tractus solitarii through a stereo‐taxically positioned microdialysis probe (active exchange length, 180–200 µm; diameter, 220 µm) for 1 h elicited an enhancement of the baroreceptor reflex response. This facilitatory effect correlated positively, during the 60‐min infusion period, with the time course of increase in the extracellular concentration of substance P and noradrenaline in the nucleus tractus solitarii. Experimentally elevating the concentration of noradrenaline at this medullary nucleus also augmented the baroreceptor reflex sensitivity. On the other hand, depletion of the noradrenergic fibers and nerve terminals at the nucleus tractus solitarii with DSP4 diminished the enhancement of baroreceptor reflex response and the corresponding elevation in extracellular concentration of noradrenaline by substance P. Microinfusion of noradrenaline into the nucleus tractus solitarii in DSP4‐treated animals, however, potentiated the baroreceptor reflex response. These results suggest that the enhancement of baroreceptor reflex response by substance P may involve an increase in the concentration of noradrenaline at the nucleus tractus solitarii via a presynaptic mechanism.