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D J Reis

Publications and source records attributed to D J Reis.

At least 127 records · Page 7Linked to original sources
PubMed1994

A single transmitter regulates gene expression through two separate mechanisms: cholinergic regulation of phenylethanolamine N-methyltransferase mRNA via nicotinic and muscarinic pathways.

ACh regulates the gene encoding phenylethanolamine N-methyltransferase (PNMT) in bovine adrenal chromaffin cells. In addition to stimulating catecholamine release from these cells, cholinergic agents elevate transcription of the PNMT gene. Carbachol, which activates both nicotinic and muscarinic receptors, produces 12-19-fold increases in PNMT mRNA and a 22-fold increase in epinephrine release. Selective nicotinic and muscarinic antagonists (hexamethonium and atropine) each partially reduce carbachol-stimulated increases in PNMT mRNA while a combination of both eliminates > 90% of the carbachol response, thus indicating that separable nicotinic and muscarinic components contribute to the cholinergic increase in PNMT mRNA. Muscarine alone produces a dose-dependent increase (mean sixfold) in steady state PNMT mRNA levels and stimulates the rate of transcription fivefold. Only atropine and the m3-m4-selective muscarinic antagonist 4-diphenylacetoxy-4-methyl-piperidine (4-DAMP) reduce the response to muscarine, strongly suggesting that the m4 receptor is crucial for PNMT mRNA activation. In these chromaffin cells, muscarine inhibits adenylate cyclase, antagonist bind with affinities characteristic of m4 receptors, and cDNA hybridization detects only m4 mRNAs (Fernando et al., 1991). Nicotine also induces a dose-dependent increase (mean of 8.5-fold) in PNMT mRNA levels. The importance of voltage-gated Ca2+ channels in the nicotine effect is demonstrated by the stimulatory effects of calcium ionophores on PNMT mRNA levels (two-to fivefold increase) and the ability of the L- and N-type channel blockers nifedipine and omega-conotoxin to decrease the nicotine response (by 60% and 40%, respectively). Nuclear "run-on" assays further reveal that nicotine enhances transcription of the PNMT gene (approximately fourfold). Thus, this study provides the first demonstration that both nicotinic and muscarinic stimulation modify genomic responses of bovine adrenergic chromaffin cells and identifies possible mechanisms.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Sympatho-excitatory neurons of the rostral ventrolateral medulla are oxygen sensors and essential elements in the tonic and reflex control of the systemic and cerebral circulations.

MEDULLARY ROSTRAL VENTROLATERAL RETICULAR NUCLEUS (RVL): Reticulospinal neurons are critical to control of the circulation by the brain. Its actions are implemented by a few reticulospinal neurons, 200 in the rat. These directly innervate and excite preganglionic sympathetic neurons of the spinal cord by releasing L-glutamate. The RVL-spinal sympathetic premotor neurons are innervated by neurochemically diverse afferents from local and remote sources. They maintain arterial pressure tonically, mediate vasomotor reflexes elicited by stimulation of baro- or chemoreceptors or in response to pain or muscular exercise, and couple vasomotor responses to defense and conditioned fear behaviors. RVL-spinal neurons are central oxygen sensors, directly excited by hypoxia, and initiate sympathetic responses to cerebral ischemia or distortion (Cushing reflex). Stimulation of the RVL directly elevates cerebral flow independently of metabolism and initiates much of the cerebrovascular vasodilation in response to hypoxemia. RVL-SPINAL NEURONS IN RELATION TO HYPERTENSION AND SHOCK: RVL-spinal neurons are sites of action for many centrally acting antihypertensive drugs and some vasoactive hormones. Their integrity is required for expression of the elevated arterial pressure in neurogenic hypertension and for the compensatory sympathetic responses to hemorrhage. We propose that RVL-spinal neurons (1) maintain the activity of sympathetic neurons in mid-range amplifying, thereby, their signaling capacities; (2) initiate and integrate circulatory responses to a lack of oxygen so as to protect the brain from real or threatened hypoxia; (3) maintain, by tonic activity, normal expression of genes and gene products of central and peripheral sympathetic neurons and their peripheral targets that relate to their structure and neurotransmission-associated functions.

Adrenergic Fibers↗
PubMed1994

Afferents to the midline thalamus issue collaterals to the nucleus tractus solitarii: an anatomical basis for thalamic and visceral reflex integration.

The goal of this study was to establish a structural basis for thalamic and visceral integration. We sought to define neural networks that convey visceral or integrated environmental stimuli to the diffuse thalamocortical relay system and that link periodic changes in forebrain and visceral reflex function. Our experiments were designed to determine whether afferents to the midline-intralaminar thalamic nuclei (MIT) issue collaterals to the general viscerosensory division of the nucleus tractus solitarii (NTS). Experiments were performed on anesthetized male Sprague-Dawley rats. Two tracers, FluoroGold and rhodamine latex microbeads, were stereotaxically centered on the MIT and NTS, respectively, in each animal. Subsets of midline thalamic afferents were identified that issue collaterals to the solitary complex. In the cerebral cortex, dually labeled soma were detected in layer V of the insular and infralimbic areas. In the subcortical forebrain, the lateral septal nucleus, anterolateral area of the bed nuclei of stria terminalis, medial preoptic nucleus, medial and central amygdaloid nuclei, caudal lateral hypothalamic area, supramammillary nucleus, and parvicellular division of the paraventricular hypothalamic nucleus constitute other newly identified sources of collateral projection. In the midbrain and pons, collateral projection cells were observed in the periaqueductal gray, dorsal raphe nucleus, mesencephalic reticular formation, laterodorsal tegmental nucleus, lateral and medial parabrachial nuclei, and noradrenergic A5 area. In the lateral parabrachial nucleus, dually labeled neurons were detected in the dorsal-lateral division. In the medulla, collaterals are derived from cells in the rostral and caudal ventrolateral reticular formation and parapyramidal area. Dually labeled cells were also found in the cerebellar fastigial nucleus. Collaterals may coordinate changes in visceral reflex excitability and thalamocortical rhythms during phases of sleep-wake cycle and behavioral expression.

Animals↗
PubMed1993

Projections from the nucleus tractus solitarii to the spinal cord.

Projections from the nucleus tractus solitarii (NTS) to the spinal cord were demonstrated in the male Sprague-Dawley rat. In retrograde transport studies, a horseradish peroxidase conjugate or a fluorescent dye, FluoroGold, were injected into midcervical or upper thoracic spinal segments. Most solitariospinal neurons were multipolar or bipolar and located between the obex and spinomedullary junction. Solitariospinal neurons were concentrated in proximity to the ventral border of the solitary tract and extended dorsally into the intermediate division and ventrolaterally into the intermediate reticular zone (IRt) of the lateral tegmental field. This subgroup predominantly projects to midcervical spinal segments. A subset of small neurons was retrogradely labeled from cervical or thoracic spinal segments in the medial commissural nucleus and contiguous with a periventricular group surrounding the central canal. In anterograde transport studies, iontophoretic deposits of Phaseolus vulgaris leucoagglutinin were centered stereotaxically on sites in NTS identified by retrograde transport data. The lectin was incorporated by neurons of the solitary complex and transported bilaterally by axons that emerged from the nucleus and entered the reticular formation. The solitario-reticular (transtegmental) pathway irradiated diagonally across the IRt and extended caudally into the cervical lateral funiculus and spinal gray. A small periventricular-spinal pathway also descended longitudinally to the neuraxis. Solitariospinal neurons project to superficial lamina of the dorsal horn, laminae VII and X and ventral horn. The projections are predominantly contralateral to phrenic and intercostal motor nuclei and ipsilateral to the intermediolateral cell column. The solitariospinal projection represents the shortest route in the central nervous system, other than the local intraspinal reflex, through which first order visceral afferents signal cardiorespiratory and alimentary motor nuclei.

Animals↗
PubMed1993

Hypoxic excitation of medullary vasomotor neurons in rats are not mediated by glutamate or nitric oxide.

Ischemic-hypoxic neuro-excitation and toxicity have been attributed to a rapid release of glutamate and formation of nitric oxide. We have now demonstrated that sympatho-excitatory response (1.2-fold increase in sympathetic nerve activity) induced by intratracheal administration of 100% N2 for 20 s in anesthetized rats and membrane inward currents (0.4-0.5 nA) induced by cyanide (300 microM) and hypoxia (saturated with 75% N2) of these neurons recorded in slices of rat rostral ventrolateral medulla were neither reduced by blocking glutamate receptors with kynurenate, synaptic transmission with tetrodotoxin nor by inhibiting nitric oxide synthase with N-nitro-L-arginine, indicating that glutamate, synaptic inputs, and nitric oxide are not involved in rapid responses of reticulospinal vasomotor neurons to hypoxia.

2-Amino-5-phosphonovalerate↗
PubMed1993

Ultrastructural localization and afferent sources of corticotropin-releasing factor in the rat rostral ventrolateral medulla: implications for central cardiovascular regulation.

We investigated the ultrastructural localization, afferent sources, and arterial pressure effects of corticotropin-releasing factor (CRF) in the nucleus reticularis rostroventrolateralis (RVL), a region of the ventrolateral medulla containing C1 adrenergic neurons and sympatho-excitatory reticulospinal afferents to sympathetic preganglionic neurons. A polyclonal antibody to CRF was localized in acrolein-fixed sections through the rat RVL by the peroxidase-antiperoxidase (PAP) method. Light microscopy showed that 1-7 perikarya/30 micron section and numerous varicose processes contained CRF-like immunoreactivity (CRF-LI). By electron microscopy, CRF-LI was most intensely localized to large (80-100 nm) dense-core vesicles within numerous terminals and a few perikarya and large dendrites. Approximately half of the terminals containing CRF-LI were in direct contact with unlabeled perikarya or dendrites; the remainder were in apposition to either unlabeled terminals or astrocytes. Most synaptic specializations were asymmetric synapses on small, unlabeled dendrites. To examine potential extrinsic sources of CRF-containing terminals in the C1 area of the RVL, PAP immunocytochemical localization of CRF was combined with retrograde transport of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP). In all cases examined, a number of dually labeled neurons were found in the paraventricular nucleus (PVN) of the hypothalamus and a few dually labeled neurons were observed in the nuclei of the solitary tract; these labeled neurons were ipsilateral to the unilateral injection of WGA-HRP into the C1 area. Fewer dually labeled perikarya were detected in the lateral hypothalamic area and the lateral parabrachial nuclei, ipsilateral to the WGA-HRP injection. Additional physiological studies showed that bilateral microinjections of CRF into the C1 area of the RVL of urethane-anesthetized rats elicited a dose-related increase in arterial pressure. The results suggest that within the C1 area of the RVL, CRF released from terminals, arising predominantly from the PVN of the hypothalamus and probably from local neurons as well, may excite sympathoexcitatory reticulospinal neurons.

Afferent Pathways↗
PubMed1993

Antisense oligodeoxynucleotides to NMDA-R1 receptor channel protect cortical neurons from excitotoxicity and reduce focal ischaemic infarctions.

The excitatory amino acid, L-glutamate, acting through its N-methyl-D-aspartate (NMDA) receptor, may contribute to neuronal death following cerebral vascular occlusion. In support of this hypothesis, NMDA receptor antagonists reduce the volume of infarction produced by occlusion of the middle cerebral artery in vivo and attenuate Ca2+ influx and neuronal death elicited by L-glutamate or NMDA in vitro. A complementary DNA coding for a major component of the NMDA receptor channel complex, a single protein of M(r) 105.5K (NMDA-R1), has been isolated from rat brain. Here we demonstrate that inhibition of the synthesis of NMDA-R1 by treatment with antisense oligodeoxynucleotides selectively reduces the expression of NMDA receptors, prevents the neurotoxicity elicited by NMDA in vitro and reduces the volume of the focal ischaemic infarction produced by occlusion of the middle cerebral artery in the rat.

Animals↗
PubMed1993

Extracellular H+ iontophoresis modifies responses to gamma-aminobutyric acid and cyanide of reticulospinal vasomotor neurons in rats.

Responses of reticulospinal vasomotor neurons, recorded in the rostral ventrolateral reticular nucleus of the medulla oblongata, to gamma-aminobutyric acid (GABA) and cyanide microiontophoreses were examined during H+ iontophoresis in anesthetized rats. Extracellular H+ iontophoresis attenuated GABA-evoked decreases and enhanced cyanide-induced increases in the neuronal activity, but had no effect on the neuronal activity when applied alone. Opposite responses were produced during OH- iontophoresis. Similar effects were also observed on the glycine-evoked inhibition of these neurons during H+ and OH- iontophoreses, suggesting that H+ modulation of the GABA-evoked inhibition may not result from a specific action at the GABA receptor-channel complex. It is concluded that extracellular H+ ions exert a modulatory action on responses of the reticulospinal vasomotor neurons to other neuro-active substances and may significantly contribute to hypoxic-ischemic cardiovascular regulation.

Animals↗
PubMed1993

Differential responses of barosensitive neurons of rostral ventrolateral medulla to hypoxia in rats.

We examined the responses to hypoxia of 48 spontaneously active barosensitive neurons of the rostral ventrolateral medulla (RVL) of anesthetized rats. Twenty-nine projected to the spinal cord while 19 did not. All spinal barosensitive neurons increased their discharges in advance of an elevation of arterial pressure in the presence or absence of arterial chemoreceptors. In contrast, 18/19 of the non-spinal barosensitive neurons were not excited by hypoxia. The results indicate that barosensitive RVL neurons consist of two populations differing in efferent pathway and responsivity to hypoxia and that the spinal barosensitive RVL neurons are functionally discrete and selectively sensitive to hypoxia.

Animals↗
PubMed1993

Expression of non-adrenergic imidazoline sites in chromaffin cells and mitochondrial membranes of bovine adrenal medulla.

We sought to characterize the non-adrenergic binding site for imidazolines, the imidazoline receptor in whole membranes and subcellular compartments of chromaffin cells of bovine adrenal medulla. [3H]Idazoxan exhibited saturable and high affinity (KD = 5 nM) binding to chromaffin cell membranes fully displaceable by idazoxan and cirazoline but not by epinephrine or rauwolscine. Binding sites were highly enriched in mitochondrial but not plasma membranes and absent from nuclear fractions. The rank order of potency for displacement of [3H]idazoxan from mitochondrial membranes was: cirazoline > idazoxan > naphazoline > amiloride > detomedine > clonidine >> phentolamine > cimetidine = imidazole 4-acetic acid > p-iodoclonidine = epinephrine = norepinephrine = rauwolscine. Binding was also inhibited with high affinity by the purported endogenous ligand clonidine-displacing substance and by K+ and the K(+)-channel antagonists 4-aminopyridine and tetraethylammonium bromide but not Na+. We conclude that: (a) adrenal chromaffin cells express imidazoline receptors but not alpha 2-adrenergic receptors; (b) these sites are predominantly localized to adrenal medullary mitochondria; and (c) imidazoline receptors conform to an idazoxan preferring (I-2) rather than the clonidine preferring (I-1) subclass and are amiloride sensitive. The data support the view that alpha 2-adrenergic and imidazoline receptors are distinct receptor species and that adrenal chromaffin cells would be a useful cultured cell system, expressing only imidazoline receptors, for further molecular and functional studies of the receptors.

Adrenal Medulla↗
PubMed1993

Expression of non-adrenergic imidazoline sites in rat cerebral cortical astrocytes.

Clonidine and related imidazoline agents, beside binding to alpha 2-adrenergic receptors, have been shown to bind to a non-adrenergic site (imidazoline sites) in brain and peripheral tissues. However, which cell types in brain, namely neurons or glia, express this binding site and the cellular effects of activation of this site are not known. We investigated the cellular localization of imidazoline binding sites in cultured rat cortical astrocytes and neurons. Membranes prepared from cultured astrocytes showed specific, high affinity binding (KD: 4 nM) for 3H-idazoxan with about tenfold higher number of binding sites than alpha 2-adrenergic sites (Bmax: 220 vs. 20 fmol/mg protein). Displacement studies exhibited the rank order of potency: cirazoline > idazoxan > amiloride > clonidine >>> epinephrine = ruawolscine defining this site as I-2a subtype of imidazoline binding sites. Moreover, the binding was inhibited by K+ but not by Na+, another characteristic of imidazoline binding sites. In contrast, membranes prepared from cultured neurons showed fewer binding sites for 3H-idazoxan that were completely displayed by adrenergic agents. Incubation of astrocytes with idazoxan, but not rauwolscine, resulted in a concentration-dependent increase in the levels of mRNA for the astrocyte specific molecule glial fibrillary acidic protein. We conclude that (a) the non-adrenergic imidazoline binding sites are expressed in astrocytes but not in neurons in rat cerebral cortex and (b) these "receptors" may influence astrocyte physiology by regulating the levels of GFAP.

Animals↗
PubMed1993

Vasopressinergic mechanisms in the nucleus reticularis lateralis in blood pressure control.

We sought to determine whether arginine vasopressin (AVP) modulates arterial pressure (AP) by a receptor-mediated action in the nucleus reticularis rostroventrolateralis (nRVL). Immunocytochemical labeling with an antiserum against a synthetic AVP conjugate revealed a discrete although modest presumptive neuropeptidergic innervation of the nRVL. Electron microscopic analysis of vasopressinergic processes in the nRVL revealed that AVP-like immunoreactivity (AVP-LI) was primarily in axons and axon terminals. Immunoreactive terminals contained numerous small clear vesicles and large dense core vesicles and formed synapses with unlabeled dendrites. In the nRVL, retrograde transport-immunofluorescence data demonstrated close appositions between vasopressinergic beaded processes and a compact subambigual column of reticulospinal neurons labeled by deposits of cholera toxin beta-subunit into the thoracic spinal cord. Similar methods were used to define the origins of the AVP-afferent projection to nRVL. These retrograde transport-immunofluorescence studies demonstrated numerous retrogradely labeled neurons in the hypothalamus, including the paraventricular nucleus (PVN), after injections of a retrograde tracer, Fluoro-Gold into the ventrolateral medulla. However, double-labeled neurons were rare and confirmed a diffuse AVP afferent innervation of the sympathoexcitatory area. Microinjection of AVP into the nRVL in anesthetized rats produced a large dose-related increase in AP different from control at a dose of 1 pmol or higher. AVP injected intravenously elevated AP only at significantly higher doses. Microinjections of AVP into the nucleus tractus solitarii (NTS) had a smaller effect whereas into the caudal ventrolateral medulla exerted no effect on AP. Bilateral microinjections of an AVP antagonist, d(CH2)5[Tyr(Me)2]AVP into the nRVL produced no change in AP but blocked the increase produced by subsequent injections of AVP. An acute hemorrhage produced by withdrawal of 2 ml of blood from the femoral vein did not alter AP. However, bilateral microinjections of the AVP antagonist into the nRVL 5 min after hemorrhage decreased AP. In contrast, the AVP-antagonist injected intravenously after hemorrhage had no effect on AP. Our data suggest that under conditions demanding increased sympathetic drive to maintain AP, such as hemorrhage, a functional AVP receptor mechanism via terminals in the nRVL may be activated to restore normal levels of AP.

Animals↗
PubMed1993

Synthesis of nitric oxide in CNS glial cells.

Attention has focused on particular neurons as the source of nitric oxide (NO) within the parenchyma of the CNS. In contrast, glial cells have been viewed mainly as potential reservoirs of L-arginine, the substrate for nitric oxide synthase (NOS), and as likely targets for neuronally derived NO because of their proximity and their expression of soluble guanylyl cyclase (sGC). However, it is becoming evident that astrocytes display both constitutive and inducible NOS activity under various conditions, and that activated microglia express an inducible NOS. The NO-producing capacity of oligodendrocytes is not yet known. Glial-derived NO has significant implications for CNS pathophysiology, given the anatomical location and abundance of these cells, and the wide variety of potential interactions that NO can have with cellular biochemistry. Our intention here is to evaluate the evidence for NO production from non-neuronal CNS sources and thus prompt discussion about potential 'nitrinergic' roles for glial cells.

Amino Acid Oxidoreductases↗
PubMed1993

Reductions in focal ischemic infarctions elicited from cerebellar fastigial nucleus do not result from elevations in cerebral blood flow.

To determine whether the neuroprotection elicited from electrical stimulation of the cerebellar fastigial nucleus (FN) is attributable to the elevation in regional cerebral blood flow (rCBF), we compared the effects in spontaneously hypertensive rats of stimulation of the rostral ventrolateral medulla (RVL) or FN on (a) a focal ischemic lesion produced by middle cerebral artery (MCA) occlusion, and (b) the changes in rCBF, measured by laser-Doppler flowmetry for 1.5 h, over regions corresponding to the ischemic core (parietal cortex), penumbra (occipital cortex), and nonischemic area (contralateral parietal cortex). Stimulation of FN for 1 h following MCA occlusion reduced infarction 24 h later by 52%. Stimulation of RVL was ineffective. Changes in the lesion were confined to the penumbra. FN and RVL stimulation comparably and significantly increased rCBF up to 185% in unlesioned animals. Following MCA occlusion, stimulation of FN or RVL and hypercarbia failed to elevate rCBF in the ischemic area but did so in the nonischemic area, even though in the same animals only FN stimulation reduced infarction 24 h later. We conclude that (a) the neuroprotection elicited from FN is not the result of an increase in rCBF but results from another mechanism, possibly reduction of metabolism in penumbra, and (b) the pathways mediating central neurogenic vasodilation and neuroprotection are, in part, distinct.

Animals↗
PubMed1993

Norepinephrine suppresses inducible nitric oxide synthase activity in rat astroglial cultures.

Exposure of primary rat astrocyte cultures to bacterial endotoxin lipopolysaccharide (LPS) causes expression of a Ca(2+)-independent form of nitric oxide synthase (NOS). In these cells, the presence of norepinephrine (NE) caused a dose-dependent inhibition of the LPS induction of NOS activity, with an IC50 value of 100 nM and significant suppression at 100 pM. Short incubations (5-40 min) with NE were as effective as 24-h continuous exposure, and inhibition was observed up to the longest incubation period measured (56 h). In contrast, previously induced NOS activity was not affected by exposure to NE. The effects of NE were mediated primarily by binding to beta-adrenergic receptors (beta-ARs) because (a) the beta-AR antagonist propranolol, but not the alpha-AR antagonist phentolamine, could reverse the effects of NE; (b) the beta-AR agonist isoproterenol, but not the alpha-AR agonist phenylephrine, was as effective as NE in blocking the effects of LPS; and (c) incubation with the cyclic AMP analogue dibutyryl cyclic AMP replicated the effects of NE. In contrast to astroglial cultures, LPS induction of NOS activity in RAW 264.7 macrophage cells was not affected by NE or dibutyryl cyclic AMP. These results indicate that in brain, inducible NOS in astrocytes can be regulated by neurotransmitter binding to glial receptors.

Amino Acid Oxidoreductases↗
PubMed1993

Mitogenic effects of ATP on vascular smooth muscle cells vs. other growth factors and sympathetic cotransmitters.

The sympathetic nervous system has been shown to exert a trophic influence on vascular smooth muscle cells (VSMC). Therefore, we studied the growth-regulating effects of the sympathetic cotransmitters ATP, neuropeptide Y (NPY), and norepinephrine (NE). ATP in concentrations of 1-100 microM greatly increased the incorporation of [3H]thymidine in VSMC from rat aorta and vena cava. ATP also increased cell number and total protein content. The maximal effect on [3H]thymidine incorporation was greater than for epidermal growth factor (20 ng/ml) or insulin (1 microgram/ml) and approximately one-half that of 10% fetal calf serum. The potency series of other nucleotides and analogues of ATP was ATP > beta, gamma-methyleneATP (AMP-PCP) > ADP > adenosine > alpha, beta- methyleneATP (AMP-CPP) > 2-methylthioATP, indicating involvement of a P2 receptor, however, it does not meet proposed pharmacological criteria of either the P2x or P2y subclass. Several proposed P2 receptor antagonists were without effect. The effect of ATP could be mediated by a "nucleotide receptor," since UTP also stimulated [3H]thymidine incorporation. In our model, there was a strong correlation between the mitogenic effects of ATP, AMP-CPP, AMP-PCP, and UTP and their ability to stimulate influx of extracellular Ca2+ (Ca2+o). Moreover, the mitogenic effect of ATP was increased by high concentrations of Ca2+o. Taken together with data showing the lack of involvement of several other second-messenger systems, this indicates a critical role for Ca2+o in mediating the mitogenic effects of ATP. Amiloride, known to inhibit the action of several growth factors, also inhibited ATP-induced mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Identification of baroreceptor reflex interneurons in the caudal ventrolateral medulla.

Interrupting neuronal activity in the caudal ventrolateral medulla (CVL) abolishes baroreceptor-mediated sympathoinhibition and vasodepressor responses. In the present study we identified CVL neurons that function as interneurons in the baroreceptor reflex arc. The mean antidromic onset latency of CVL neurons (5 ms) after stimulation in the rostral ventrolateral medulla (RVL) suggests that they transmit information to the RVL via unmyelinated axons. Stimulation of baroreceptor afferents in the aortic depressor nerve (ADN) excited CVL neurons projecting to the RVL with onset latencies between 15 and 45 ms. The short-latency ADN stimulus-evoked excitation of CVL barosensory interneurons preceded the onset of the ADN stimulus-evoked inhibition of RVL-spinal sympathoexcitatory neurons. Longer-latency ADN-evoked CVL neuronal responses may arise from activation of unmyelinated ADN afferents that can prolong the inhibition of RVL sympathoexcitatory neurons. The excitation of CVL barosensory interneurons resulting from the systolic pressure rise was followed by a period of decreased excitability of RVL sympatho-excitatory neurons, which was of comparable duration to the increase in the discharge probability of CVL neurons. Our characterization of baroreceptor reflex interneurons in the CVL suggests that transmission of baroreceptor information involves a complex activation of medullary interneurons responding selectively to different aspects of the arterial pressure stimulus.

Animals↗