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Yoshimi Misu - One of the best experts on this subject based on the ideXlab platform.
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is l dopa a neurotransmitter of the primary baroreceptor afferents terminating in the nucleus tractus solitarii of rats
Advances in pharmacology, 1997Co-Authors: Yoshimi Misu, Yoshio Goshima, Jinliang Yue, Takeaki MiyamaeAbstract:Publisher Summary Transmitter-like Dihydroxyphenylalanine (DOPA) is released from rat striata and blood pressure regulation centers in the lower brain stem. Exogenous DOPA itself elicits in vitro presynaptic and in vivo postsynaptic responses. All are stereoselective, and most are antagonized by DOPA methyl ester, a competitive DOPA antagonist. DOPA does not displace selective binding of α2, β, D1, and D2 ligands in brain membrane preparations. It is possible to cooperate for effectiveness in Parkinson's disease. Meanwhile, DOPA induces DOPA ester-sensitive neuronal glutamate release from slices, even under inhibition of aromatic L-amino acid decarboxylase (AADC). The release by baroreceptor stimulation with phenylephrine has been abolished by bilateral sinoAortic denervation without modification of hypertension. DOPA microinjected into depressor sites of the medial nucleus tractus solitarii (NTS) identified by prior glutamate leads to dose-dependent decreases in blood pressure and heart rate (HR) in untreated rats and in those treated with central AADC inhibitor. The discussion also includes interactions between DOPAergic and GABAergic systems. GABA is an inhibitory neuromodulator for baroreflex at the level of NTS. GABA functions tonically via GABAA receptors to elicit increases in blood pressure and HR and to inhibit decreases in those by electrical Aortic Nerve stimulation. The third topic under discussion in this chapter is altered functions of the DOPA system in the NTS of adult spontaneously hypertensive rats (SHR). Basal DOPA release is lower in SHR than age-matched Wistar-Kyoto (WKY) rats. This release has been reduced by tetrodotoxin (TTX) to the same absolute levels in the two strains.
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baroreceptor Aortic Nerve mediated release of endogenous l 3 4 dihydroxyphenylalanine and its tonic depressor function in the nucleus tractus solitarii of rats
Neuroscience, 1994Co-Authors: Jinliang Yue, Yoshio Goshima, H Okamura, Shinichi Nakamura, M Geffard, Yoshimi MisuAbstract:Abstract We have proposed that l -3,4-dihydroxyphenylalanine ( l -DOPA) is a neurotransmitter and/or neuromodulator in the central nervous system [Misu Y. and Goshima Y. (1993) Trends pharmac. Sci. 14, 119–123]. This study aimed to explore whether or not endogenous l -DOPA, as a neurotransmitter candidate of the primary baroreceptor afferents, tonically functions to activate depressor neurons in the nucleus tractus solitarii of anesthetized rats. By parallel microdialysis in bilateral nucleus tractus solitarii areas, the basal l -DOPA release was in part inhibited by tetrodotoxin perfusion (1 μM) or Ca2+ deprivation, and was markedly reduced by α-methyl-p-tyrosine(200mg/kg, i.p.), a tyrosine hydroxylase inhibitor. Forty to 100 mM K+ concentration-dependently released l -DOPA. Fifty millimoles K+ repetitively and constantly released l -DOPA. This release was Ca2+-dependent. Stimulation of the left Aortic Nerve (100 Hz, 8 V) repetitively and constantly released l -DOPA and this release was tetrodotoxinsensitive. Phenylephrine i.v. infused produced l -DOPA release and reflex bradycardia, temporally associated with a rise and subsequent recovery of blood pressure. This release and bradycardia were abolished by denervation of the bilateral carotid sinus and Aortic Nerves. In addition, l -DOPA methyl ester, a competitive l -DOPA antagonist, when microinjected into depressor sites of the left nucleus tractus solitarii, antagonized depressor responses to mild stimulation (20 Hz, 3 V) of the ipsilateral Aortic Nerve. This antagonist alone, microinjected bilaterally, elicited a dose-dependent hypertension, which was abolished by α-methyl-p-tyrosine. Furthermore, by immunocytochemical analysis seven days after denervation of the left Aortic Nerve, tyrosine hydroxylase- and l -DOPA-, but not dopamine- and dopamine-β-hydroxylase-immunoreactivities decreased in the ipsilateral nucleus tractus solitarii and dorsal motor vagus nucleus complex area. In the left ganglion nodosum, denervation decreased staining and number of l -DOPA-immunoreactive cells and staining of tyrosine hydroxylase-immunoreactive cells, but no modification of dopamine-immunoreactive cells was seen. Taken together with previous findings that l -DOPA itself is stereoselectively responsible for cardiovascular control in this nucleus, it is probable that l -DOPA is a neurotransmitter of the primary baroreceptor afferents terminating directly in depressor neurons and/or indirectly in some neurons within a microcircuit, including depressor neurons of the nucleus tractus solitarii. Endogenously released l -DOPA itself tonically functions to activate depressor neurons for regulation of blood pressure in the rat nucleus tractus solitarii.
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Ipsilateral but not contralateral blockade of excitatory amino acid receptors in the caudal ventrolateral medulla inhibits Aortic baroreceptor reflex in rats
Naunyn-Schmiedeberg's archives of pharmacology, 1991Co-Authors: Takao Kubo, M. Kihara, Yoshimi MisuAbstract:The caudal ventrolateral medulla (CVLM) contains vasodepressor neurons which, when activated, decrease vasomotor tone. To investigate whether excitatory amino acid receptors in the CVLM of the rat are involved in mediation of the Aortic baroreceptor reflex, we microinjected amino acid antagonists unilaterally into the CVLM and examined their effects on the depressor response to electrical stimulation of the Aortic Nerve which contains mainly baroreceptor afferent fibers in rats. Male Wistar rats were anaesthetized with urethane, paralyzed and artificially ventilated. To block reflex vagal effects, methylatropine (1 mg/kg) was given intravenously. Kynurenate (227 ng), an excitatory amino acid antagonist, injected ipsilaterally but not contralaterally into the CVLM markedly inhibited the depressor response to Aortic Nerve stimulation, while both injections produced a similar small increase in basal blood pressure. Muscimol (1 ng), a GABA receptor agonist, injected ipsilaterally into the CVLM partly inhibited the baroreflex response, while it produced a moderate increase in basal blood pressure. 2-Amino-5-phosphonovalerate (APV) (10 ng), a N-methyl-d-aspartate (NMDA) receptor antagonist, and MK-801 (30 ng), a NMDA receptor channel blocker, partly inhibited the baroreflex response. MK-801 (30 ng) injected into the CVLM reduced the depressor response to the NMDA receptor agonist NMDA (0.3 ng) but not to the quisqualate receptor agonist quisqualate (0.1 ng) and the kainate receptor agonist kainate (0.1 ng), while kynurenate (227 ng) inhibited the depressor response to all three excitatory amino acid receptor agonists. These findings provide further evidence for the presence of excitatory amino acid receptors involved in mediating the Aortic baroreceptor reflex in the rat CVLM. It appears that neurons other than the vasodepressor neurons in the CVLM, at least in part, play a role in transmitting the Aortic baroreceptor reflex. In addition, both NMDA and non-NMDA receptors may be responsible for the mediation of the reflex.
Steven W. Mifflin - One of the best experts on this subject based on the ideXlab platform.
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subthreshold Aortic Nerve inputs to neurons in nucleus of the solitary tract
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2000Co-Authors: Jing Zhang, Steven W. MifflinAbstract:Subthreshold Aortic Nerve (AN) inputs to neurons receiving a monosynaptic AN-evoked input (MSNs: respond to each of two AN stimuli separated by 5 ms) and neurons receiving a polysynaptic AN input (...
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temporal processing of Aortic Nerve evoked activity in the nucleus of the solitary tract
Journal of Neurophysiology, 1996Co-Authors: Deborah A Scheuer, Jing Zhang, Glenn M. Toney, Steven W. MifflinAbstract:1. Temporal processing of heterogenous afferent signals by nucleus of the solitary tract (NTS) neurons has been previously characterized. Experiments were performed in 26 pentobarbital-sodium-anest...
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Time-dependent inhibition of hindlimb somatic afferent inputs to nucleus tractus solitarius.
Journal of Neurophysiology, 1994Co-Authors: Glenn M. Toney, Steven W. MifflinAbstract:: 1. In the present investigation, experiments were performed in anesthetized, paralyzed rats (n = 40) to 1) identify and characterize responses of nucleus tractus solitarius (NTS) neurons to hindlimb somatic afferent inputs; 2) determine if hindlimb somatic inputs to NTS undergo time-dependent inhibition similar to that observed among visceral afferent inputs; and 3) determine if somatic afferent-evoked NTS unit discharge is altered by activation of baroreceptor afferent inputs. 2. Extracellular discharge was recorded from single NTS units following electrical stimulation (approximately 500 microA) of the contralateral tibial Nerve (TN) (skeletal muscle afferents), sural Nerve (SN) (cutaneous afferents), and the ipsilateral Aortic Nerve (AN) (baroreceptor afferents). To identify possible time-dependent interactions, a paired pulse or conditioning-test stimulation procedure was employed. The activity of NTS neurons was recorded in response to test stimuli delivered to either TN or SN first in the absence and then in the presence of conditioning stimuli delivered to TN, SN, or AN 50, 150, and 250 ms before the test stimuli. 3. The results indicate that among 31 NTS cells activated by somatic Nerve stimulation, 14 (approximately 50%) received convergent inputs from both the TN and SN, 9 responded to TN stimulation only and 2 were activated by SN stimulation only. These cells were not spontaneously active but showed two distinct patterns of evoked discharge. Some had only a short latency, unimodal response that averaged 25.5 +/- 2.0 (SE) ms for TN inputs (n = 21) and 27.9 +/- 2.8 ms for SN inputs (n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)
Christina Leone - One of the best experts on this subject based on the ideXlab platform.
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non nmda receptors in the nucleus of the tractus solitarius play the predominant role in mediating Aortic baroreceptor reflexes
Brain Research, 1991Co-Authors: Frank J Gordon, Christina LeoneAbstract:Abstract The purpose of these studies was to determine the relative role ofN-methyl- d -aspartic acid (NMDA) receptors and non-NMDA receptors in the nucleus of the tractus solitarius (NTS) in mediating arterial baroreceptor reflexes evoked by electrical stimulation of the Aortic Nerve. Selective blockade of NMDA receptors in the NTS had little effect on Aortic baroreflexes except at high frequencies of Aortic Nerve stimulation. In contrast, blockade of non-NMDA receptors in the NTS abolished Aortic baroreceptor reflexes. These results suggest that although NMDA receptors may modulate baroreflex responses, synaptic activation of non-NMDA receptors in the NTS plays the predominant role in mediating Aortic baroreceptor reflexes.
Claude Julien - One of the best experts on this subject based on the ideXlab platform.
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frequency response of renal sympathetic nervous activity to Aortic depressor Nerve stimulation in the anaesthetized rat
The Journal of Physiology, 2001Co-Authors: Emmanuelle Petiot, Christian Barres, Bruno Chapuis, Claude JulienAbstract:The contribution of central baroreceptor reflex pathways to the dynamic regulation of sympathetic nervous activity (SNA) has not been properly examined thus far. The aim of this study was to characterize the transfer function of the central arc of the baroreceptor reflex (from baroreceptor afferent activity to SNA) over a wide range of frequencies. In nine baroreceptor-intact and six sino-Aortic baroreceptor-denervated rats anaesthetized with urethane, the renal SNA was recorded while applying sinusoidal stimulation to the Aortic depressor Nerve at 26 discrete frequencies ranging from 0.03 to 20 Hz. At each modulation frequency, cross-power spectrum analysis using a fast Fourier transform algorithm was performed between the stimulation and renal SNA, which provided the transfer function of the central arc. In both baroreceptor intact and denervated rats, the transfer gain increased by a factor of about three between 0.03 and 1 Hz. At higher frequencies, the gain decreased but remained above the static gain of the system up to 12 Hz. There was a slight phase lead up to 0.4 Hz, then a continuously increasing phase lag. A three-element linear model satisfactorily described the experimental transfer function. The model combined a derivative gain (corner frequency ∼0.15 Hz), an overdamped second-order low-pass filter (natural frequency ∼1 Hz) and a fixed time delay (∼100 ms). These results indicate that the central arc of the baroreceptor reflex shows derivative properties that are essential for compensating the filtering of fast oscillations of baroreceptor afferent activity and thus for the generation of fast oscillations of renal SNA (e.g. those related to the cardiac cycle). The overall transfer function of the arterial baroreceptor reflex combines the properties of the so-called neural arc (from arterial pressure (AP) to sympathetic nervous activity (SNA)) and those of the so-called peripheral arc (from SNA to AP). The transfer gain of the peripheral arc shows low-pass filter properties (i.e. fluctuations of vascular resistance and thus AP, attenuate progressively as the frequency of SNA fluctuations increases: Rosenbaum & Race, 1968; Ikeda et al. 1996; Bertram et al. 2000; Guild et al. 2001). In contrast, the transfer gain of the neural arc shows high-pass filter properties (i.e. the amplitude of SNA fluctuations increases as the frequency of the pressure perturbation increases: Kezdi & Geller, 1968; Harada et al. 1992; Ikeda et al. 1996). Therefore, by amplifying SNA responses, the neural arc partly compensates for the attenuation occurring at vascular neuro-effector junctions. It has been suggested that this effect improves the efficiency of the baroreceptor reflex in correcting rapid AP perturbations (Ikeda et al. 1996). The high-pass filter (also termed rate sensitive or derivative) characteristics of the neural arc of the baroreceptor reflex can originate from arterial baroreceptors and/or from central nervous pathways. Derivative properties have been demonstrated for arterial baroreceptors using single Nerve fibre recordings in isolated rabbit carotid sinus (Franz et al. 1971) and rat Aortic arch (Brown et al. 1978) preparations. More recently, it was reported that in anaesthetized rabbits, the gain of the transfer function between pressure in the in situ isolated baroreceptor area and Aortic depressor Nerve activity increased by a factor of two to three between 0.01 and 1 Hz (Sato et al. 1998). To our knowledge, only two studies, performed on anaesthetized rabbits, examined the transfer function of the central arc (i.e. from baroreceptor afferent activity to SNA), thus excluding baroreceptor endings. In the first study (Imaizumi et al. 1994), AP was randomly perturbed by balloon inflation while recording Aortic depressor Nerve activity and renal SNA (RSNA). The gain of the transfer function from Aortic Nerve activity to RSNA was flat up to 0.3 Hz and could not be analysed at higher frequencies. In a second study, the same group described the transfer function from Aortic Nerve stimulation to RSNA (Kubo et al. 1996). The gain of the transfer function could be studied from 0.012 to 0.8 Hz and was claimed to be flat in this frequency range, although it showed a tendency to increase (see Fig. 4 in Kubo et al. 1996). From these observations it was concluded that central baroreceptor reflex pathways do not contribute to the high-pass filter characteristics of the neural arc. One major limitation to these studies is that the frequency range investigated did not include frequencies at which arterial baroreceptors are normally exposed to AP fluctuations, especially the frequency of the heart beat (typically, 3-4 Hz in rabbits and 5-6 Hz in rats) and its harmonics. Figure 4 Linear modelling of the experimental transfer function The aim of this study is to provide a more detailed description of the transfer properties of central baroreceptor reflex pathways, especially by expanding the range of frequencies investigated. We electrically stimulated the Aortic depressor Nerve in anaesthetized rats with a sinusoidal signal at discrete frequencies up to 20 Hz, while recording RSNA. We verified that this procedure allowed us to estimate correctly the open loop-transfer function by comparing data obtained in baroreceptor-intact rats and in rats after acute sino-Aortic baroreceptor denervation. Finally, we investigated whether a simple linear model could provide a proper description of the experimental transfer function.
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the arterial baroreceptor reflex of the rat exhibits positive feedback properties at the frequency of mayer waves
The Journal of Physiology, 1998Co-Authors: Delphine Bertram, Christian Barres, Guy Cuisinaud, Claude JulienAbstract:Modelling studies have led to the proposal that Mayer waves (∼0.4 Hz in rats) could result from a resonance phenomenon in a feedback control loop. In this study, we investigated the presence of a resonance frequency in the arterial baroreceptor reflex loop, i.e. a particular frequency at which arterial pressure feeds back positively to the baroreceptors. Frequency responses of mean arterial pressure (MAP) to Aortic depressor Nerve (ADN) stimulation were studied in fifteen urethane anaesthetized, ventilated rats with cardiac autonomic blockade. The ADN was stimulated using rectangular trains of impulses (2 ms, 100 Hz) delivered at frequencies ranging from 0.1 to 1 Hz. Phase angles between impulses and MAP were calculated using cross-spectral analysis based on a fast Fourier transform algorithm. Rhythmic ADN stimulation induced regular MAP oscillations at the expected frequencies that were attenuated by α-adrenoceptor blockade and abolished after ganglionic blockade. The relationship between impulse and MAP oscillations was characterized by a strong coherence and a positive phase shift at low frequencies, indicating that impulses led MAP with respect to the out-of-phase pattern. Deviation of the phase from the out-of-phase behaviour was mainly due to the presence of a fixed time delay (∼0.8 s) between ADN stimuli and MAP changes. Phase angles fell to zero at 0.42 ± 0.02 Hz. In rats, the arterial baroreceptor reflex exhibits a resonance frequency close to the frequency of spontaneously occurring Mayer waves. The reflex therefore seems the most likely origin for the Mayer waves. In almost all mammalian species studied thus far, arterial pressure-time series exhibit regular oscillations at frequencies lower than those for respiration. These low frequency oscillations are usually referred to as Mayer waves (Mayer, 1876). The average frequency is fairly constant among individuals and is close to 0.1 Hz in humans, dogs (Pagani et al. 1986) and cats (Di Rienzo et al. 1991), and 0.4 Hz in rats (Rubini et al. 1993; Brown et al. 1994). Mayer waves are usually attributed to cyclic changes in sympathetic vasomotor tone. It has been shown that Mayer waves are coupled with well-defined oscillations in the activity recorded directly from sympathetic Nerves in humans (Pagani et al. 1997) and rats (Brown et al. 1994). Moreover, in rats, Mayer waves are strongly attenuated after acute α-adrenoceptor blockade (Japundzic et al. 1990; Cerutti et al. 1991; Rubini et al. 1993) or chronic chemical sympathectomy (Cerutti et al. 1991; Daffonchio et al. 1995; Julien et al. 1995). In the past decade, Mayer waves have been the focus of a large number of studies (for review see Persson, 1997), especially because their amplitude was proposed as an indicator of sympathetic modulation of vascular tone (Malliani et al. 1991). Despite continuing effort, there is still no general agreement as to whether Mayer waves originate from the autonomous activity of a central oscillator or from a resonance phenomenon in a reflex control loop. The former hypothesis was put forward after the demonstration that in anaesthetized cats, spontaneous slow oscillations of preganglionic sympathetic nervous activity could be observed in the absence of concomitant changes in arterial pressure (Preiss & Polosa, 1974). More recently, it was reported that in vagotomized dogs, blood flow in the vascularly isolated hindlimb exhibited self-sustained oscillations even when carotid sinus pressure was held constant (Grasso et al. 1995). Although both studies suggest the involvement of a central oscillator in the genesis of Mayer waves, it must be noted that the period of the oscillations reported in these studies (20–25 s) is longer than that of the 10 s oscillations occurring spontaneously in conscious cats (Di Rienzo et al. 1991) and dogs (Pagani et al. 1986). The involvement of a resonance phenomenon in the genesis of low frequency oscillations of arterial pressure was proposed as early as 1951 by Guyton & Harris. Later on, the hypothesis was refined by introducing computer-simulated models of the short-term control of arterial pressure. It was proposed that a resonance phenomenon in the arterial baroreceptor reflex loop could generate regular, self-sustained oscillations of arterial pressure, mainly because of the delay in the vascular responses to sympathetic modulation (DeBoer et al. 1987; Madwed et al. 1989; Burgess et al. 1997b). Experimental support for this hypothesis came from studies in sino-Aortic baroreceptor denervated animals, which demonstrated a reduction in sympathetically mediated oscillations of arterial pressure (Di Rienzo et al. 1991; Cerutti et al. 1994; Jacob et al. 1995), and a selective uncoupling from corresponding fluctuations in vascular conductances (Julien et al. 1995). Although these studies strongly suggested an important role for the arterial baroreceptor reflex in the synchronization of arterial pressure oscillations in the Mayer band, they did not provide unequivocal evidence that the oscillations are actually generated by the reflex. Indeed, chronically after baroreceptor denervation, fluctuations of arterial pressure in the frequency band containing the Mayer waves are reduced by only 30–50 % (Di Rienzo et al. 1991; Cerutti et al. 1994; Julien et al. 1995). In addition, it has been shown in denervated rats that the residual oscillations in this band are of sympathetic origin, as they disappear after ganglionic blockade (Cerutti et al. 1994). These observations, therefore, are not entirely conclusive as to the exact role of arterial baroreceptors, since incomplete denervation or reinnervation of baroreceptor areas, as well as sensitization of other cardiovascular reflexes, could well account for the residual variability in the Mayer band. The aim of the present study was to determine whether the arterial baroreceptor reflex of the rat actually exhibits a resonance frequency, i.e. a particular frequency at which arterial pressure is fed back positively to the baroreceptors. We therefore characterized the phase relationship between rhythmic stimulation of the Aortic depressor Nerve and the resulting oscillations of arterial pressure. The Aortic Nerve was chosen because it contains only baroreceptor sensory afferents in the rat (Sapru et al. 1981). Because there is strong evidence that heart rate oscillations tend to oppose, rather than reinforce arterial pressure oscillations of ∼0.4 Hz in rats (Cerutti et al. 1991, 1994), all experiments were performed under cardiac autonomic blockade. Finally, to ascertain that arterial pressure oscillations induced by Aortic Nerve stimulation were mediated by the sympathetic nervous system, experiments were repeated after sequential blockade of α-adrenoceptors and ganglionic transmission.
Trevor F C Batten - One of the best experts on this subject based on the ideXlab platform.
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differential expression of vesicular glutamate transporters by vagal afferent terminals in rat nucleus of the solitary tract projections from the heart preferentially express vesicular glutamate transporter 1
Neuroscience, 2005Co-Authors: Eric K A Corbett, J K Sinfield, P N Mcwilliam, Jim Deuchars, Trevor F C BattenAbstract:The central projections and neurochemistry of vagal afferent neurones supplying the heart in the rat were investigated by injecting cholera toxin B-subunit into the pericardium. Transganglionically transported cholera toxin B-subunit was visualized in the medulla oblongata in axons and varicosities that were predominantly aggregated in the dorsomedial, dorsolateral, ventrolateral and commissural subnuclei of the caudal nucleus of the solitary tract. Unilateral vagal section in control rats prevented cholera toxin B-subunit labeling on the ipsilateral side of the nucleus of the solitary tract. Fluorescent and electron microscopic dual labeling showed colocalization of immunoreactivity for vesicular glutamate transporter 1, but only rarely vesicular glutamate transporters 2 or 3 with cholera toxin B-subunit in terminals in nucleus of the solitary tract, suggesting that cardiac vagal axons release glutamate as a neurotransmitter. In contrast, populations of vagal afferent fibers labeled by injection of cholera toxin B-subunit, tetra-methylrhodamine dextran or biotin dextran amine into the Aortic Nerve, stomach or nodose ganglion colocalized vesicular glutamate transporter 2 more frequently than vesicular glutamate transporter 1. The presence of other neurochemical markers of primary afferent neurones was examined in nucleus of the solitary tract axons and nodose ganglion cells labeled by pericardial cholera toxin B-subunit injections. Immunoreactivity for a 200-kDa neurofilament protein in many large, cholera toxin B-subunit-labeled nodose ganglion cells indicated that the cardiac afferent fibers labeled are mostly myelinated, whereas binding of Griffonia simplicifolia isolectin B4 to fewer small cholera toxin B-subunit-labeled ganglion cells suggested that tracer was also taken up by some non-myelinated axons. A few labeled nucleus of the solitary tract axons and ganglion cells were positive for substance P and calcitonin gene-related peptide, which are considered as peptide markers of nociceptive afferent neurones. These data suggest that the population of cardiac vagal afferents labeled by pericardial cholera toxin B-subunit injection is neurochemically varied, which may be related to a functional heterogeneity of baroreceptive, chemoreceptive and nociceptive afferent fibers. A high proportion of cardiac neurones appear to be glutamatergic, but differ from other vagal afferents in expressing vesicular glutamate transporter 1.