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Biomedical subjects

W T Talman

Publications and source records attributed to W T Talman.

At least 19 recordsLinked to original sources

Glycine-containing terminals in the rat dorsal vagal complex.

The present study examined the distribution of glycine and glycine-receptors in the dorsal vagal complex using pre-embedding immunocytochemistry. Glycine-immunoreactive terminals were present in moderate densities in the medial, intermediate, interstitial, commissural and ventrolateral subnuclei of the nucleus tractus solitarii. The dorsolateral nucleus tractus solitarii and the dorsal vagal motor nucleus contained only very few, scattered glycine-containing terminals. Glycine terminals appeared to be concentrated in regions of the dorsal vagal complex receiving primary vagal afferents, though previous studies have suggested that glycine is not present in these afferents. A conspicuously high concentration of glycine terminals was observed in the medial nucleus tractus solitarii where a population of cholinergic neurons has been identified previously. Ultrastructurally glycine immunoreactivity was principally associated with terminals containing flattened, pleomorphic vesicles and forming symmetrical synaptic contacts, mostly with dendrites. Glycine receptor immunoreactivity was present throughout the dorsal vagal complex with little evidence of subnuclear localization. With electron-microscopic examination, glycine receptor immunoreactivity was associated with dendritic membranes and was associated presynaptically with terminals containing flattened pleomorphic vesicles. Overall, the present data provide evidence consistent with a neurotransmitter role for glycine in the dorsal vagal complex. The presence of glycine in regions of the dorsal vagal complex receiving vagal afferents suggests a prominent role for this neurotransmitter in autonomic regulation.

Animals

Mechanisms of cardiovascular responses to glycine injected into the dorsal vagal motor nucleus in rat.

Microinjection of glycine into the dorsal vagal motor nucleus of anesthetized rats elicits increases in arterial pressure and heart rate. In the nucleus tractus solitarii, where cardiovascular responses to injection of glycine may be mediated through release of acetylcholine, there is a dense concentration of glycinergic nerve terminals and glycine receptors. In this study, using immunohistochemical methods, we show that glycine terminals and receptors are present in caudal dorsal vagal motor nucleus, although the concentration of both terminal elements is less than in adjacent nucleus tractus solitarii. Responses to glycine microinjected into the dorsal vagal motor nucleus are blocked by the muscarinic antagonist atropine microinjected at the same site; but, unlike responses to glycine in the nucleus tractus solitarii, responses to glycine in the dorsal vagal motor nucleus are not prolonged by physostigmine. These data support the possibility that endogenous glycine may play a role as a transmitter in the dorsal vagal motor nucleus. Responses to glycine may be mediated through actions at muscarinic receptors but not through acetylcholine itself.

Animals

Glycine microinjected into nucleus tractus solitarii of rat acts through cholinergic mechanisms.

Previous studies have demonstrated the release of glycine from neurotransmitter pools in the region of the nucleus tractus solitarii (NTS) where cardiovascular afferents terminate. Microinjection of glycine into NTS elicits decreases in arterial pressure and heart rate; these effects are also produced by glutamate or acetylcholine. As glycine may act both at the N-methyl-D-aspartate (NMDA)-receptor complex and centrally to release acetylcholine, we have sought to determine whether the cardiovascular responses to exogenous glycine are mediated through glutamatergic or cholinergic mechanisms. Responses to glycine microinjected into the NTS of anesthetized rats were not affected by blockade of the NMDA receptor complex but, like acetylcholine, were blocked by muscarinic receptor blockade. Physostigmine prolonged responses to glycine. Subthreshold doses of glycine, which augmented responses to acetylcholine microinjected into NTS, either decreased or had no effect on glutamate or NMDA. This study supports a role for glycine in cardiovascular regulation by the NTS and suggests that the actions of glycine may be effected, at least in part, through cholinergic mechanisms.

Acetylcholine

Cerebrovascular effects produced by electrical stimulation of fastigial nucleus.

We used the microsphere technique and laser flowmetry to assess cerebral blood flow in 43 anesthetized rats. Cerebral blood flow did not increase significantly when the fastigial nucleus was stimulated 15 min after administration of alpha-chloralose. In animals that received maintenance doses of alpha-chloralose, the modest (50%) increase in cerebral blood flow that did occur returned toward control during stimulation despite a continued stable elevation of arterial pressure. Stimulation of fastigial nucleus 2 h after alpha-chloralose elicited a 20 +/- 3 mmHg increase in arterial pressure; cerebral blood flow increased gradually for 30-60 s after the rise in arterial pressure and reached a peak that was approximately 90% (P less than 0.05) above baseline. The stimuli did not significantly reduce vascular resistance or impair autoregulation. We did not stimulate the fastigial nucleus for more than 2 h after administration of alpha-chloralose because anesthesia was effective for only 2 h. This study demonstrates that stimulation of the fastigial nucleus in rat produces a delayed increase in cerebral blood flow that is blocked by alpha-chloralose anesthesia. The delay in increases of cerebral blood flow suggests that a metabolic mechanism, not a direct neurogenic vascular effect, may account for increases in flow with fastigial stimulation.

Analysis of Variance

Cholecystokinin in nucleus tractus solitarii modulates tonic and phasic gastric pressure.

Local excitation of neurons at the site of termination of gastric vagal afferents in the nucleus tractus solitarii (NTS) alters gastric pressure. Microinjection of one putative satiety peptide bombesin into NTS increases pressure while substance P lowers it. Therefore, we sought to determine the effects of the microinjection of cholecystokinin octapeptide (CCK-8) from micropipettes placed stereotactically into the NTS of anesthetized rats with balloons placed in the gastric antrum to sense gastric pressure waves. Sulfated CCK-8, but not nonsulfated CCK-8, produced dose-dependent decreases of gastric pressure, transient blockade of phasic waves, and subsequent dysrhythmic phasic activity. The effects were specifically related to injections into NTS and did not occur with injections given intravenously, intracisternally, or into tissue adjacent to NTS. These results support a role for CCK-8 in central regulation of not only tonic gastric pressure but also phasic activity and gastric motility.

Animals

Nucleus prepositus hypoglossi. A medullary pressor region.

Electrical stimulation of fibers of passage through the fastigial nucleus increases arterial pressure. To identify nuclei that may project through the pressor region of the fastigial nucleus, we injected the retrograde tracer fast blue unilaterally at confirmed pressor sites in the nucleus. In seven rats, we found dense fluorescent labeling bilaterally in the external cuneate, lateral reticular, medial vestibular, and caudal prepositus hypoglossi nuclei, and contralaterally in the inferior olivary nucleus. There had been no reports of a cardiovascular role for the nucleus prepositus hypoglossi; thus, we sought to determine if electrical or chemical stimulation of that nucleus or the adjacent medial vestibular nucleus altered arterial pressure or heart rate in 24 anesthetized rats. Both types of stimuli to the caudal, but not the rostral, pole of the nucleus prepositus hypoglossi or to the medial vestibular nucleus elicited an increase in arterial pressure; bradycardia accompanied the former and tachycardia the latter. Both the nucleus prepositus hypoglossi and medial vestibular nucleus may participate in central cardiovascular regulation.

Animals

Altered cardiovascular responses to glutamate and acetylcholine microinjected into the nucleus tractus solitarii of the SHR.

L-glutamate (GLU) or acetylcholine (ACh) injected into the nucleus tractus solitarii (NTS) of rat elicits a decrease in arterial pressure (AP) and heart rate (HR) similar to that seen with activation of the baroreflex. Both compounds may play a role in the mediation of the baroreflex at the level of NTS. The baroreflex may be disturbed in the spontaneously hypertensive rat (SHR). Thus we sought to determine if the dose-related responses to microinjection (50 nl) of the two putative transmitters into NTS may be altered in SHR vs Wistar Kyoto (WKY) controls. Both GLU and ACh produced significant dose-related decreases in AP and HR in SHR and WKY. The dose-related changes in AP elicited by GLU were shifted significantly to the right in SHR compared to WKY. Responses of AP were only different after intermediate doses of ACh. The dose-related HR responses to GLU were the same in SHR and WKY. However, the HR response to ACh was significantly reduced in the SHR. These data suggest that cardiovascular regulation in the NTS through GLU and ACh mechanisms may be disturbed in the SHR.

Acetylcholine

Kynurenic acid microinjected into the nucleus tractus solitarius of rat blocks the arterial baroreflex but not responses to glutamate.

The selective excitatory amino acid antagonist kynurenic acid was bilaterally microinjected into the nucleus tractus solitarius of rats to determine its effects on the arterial baroreflex and on the cardiovascular responses to glutamate and nonglutamate agonists injected at the same site. Kynurenic acid blocked the responses to N-methyl-D-aspartate and kainate as well as the baroreflex, but did not block the response to glutamate, quisqualate, or acetylcholine. The data may suggest that glutamate is not a neurotransmitter in the baroreflex arc or that only certain glutamate receptors are integral to the baroreflex in the nucleus tractus solitarius.

Acetylcholine

Glycine, like glutamate, microinjected into the nucleus tractus solitarii of rat decreases arterial pressure and heart rate.

Glycinergic mechanisms have been implicated in central cardiovascular regulation. However, the inhibitory amino acid's role in the nucleus tractus solitarii (NTS), the site of termination of cardiovascular afferents, has not been clarified. Thus, we sought to determine if the microinjection of glycine into the NTS alters arterial pressure and heart rate. Microinjections of glycine, like glutamate, confined to the NTS decreased arterial pressure and heart rate in a neurally mediated, dose-dependent manner. The glycine antagonist strychnine completely blocked these effects of glycine but did not itself alter arterial pressure or heart rate, or interfere with the baroreceptor reflex. The acute hypotensive, bradycardic response to glycine was followed by a period during which glycine essentially eliminated the cardiovascular responses to the microinjection into the NTS of glutamate, an amino acid reputed to be a transmitter in the baroreceptor reflex arc. These data suggest that glycine is involved in cardiovascular regulation by the NTS but do not support its being an integral transmitter in the baroreceptor reflex.

Animals

Content and in vitro release of endogenous amino acids in the area of the nucleus of the solitary tract of the rat.

We sought to identify amino acid neurotransmitter candidates within the nucleus of the solitary tract in rats. Twenty endogenous amino acids were quantified by reverse-phase HPLC with fluorescence detection (30-fmol limit). Micropunches (1 mm) of the intermediate area of the solitary nucleus were prepared, and the amino acid content determined. Of all the components measured, the putative transmitters Glu, Gly, gamma-aminobutyric acid, taurine, Asp, and Ala appeared in greatest concentrations. Bilateral micropunches superfused in vitro with buffered medium containing 56 mM potassium released Glu, gamma-aminobutyric acid, and Gly in a significant manner (p less than 0.05) compared with basal levels. With Glu, 78% was calcium-dependent and, therefore, presumably from nerve endings; 99% of gamma-aminobutyric acid and 42% of Gly were dependent on calcium. After removal of the nodose ganglion, a bilateral decrease in the calcium-dependent release of Glu and gamma-aminobutyric acid, but not Gly, was observed; decreases were significant ipsilateral to the site of ablation. We conclude that (a) Glu is a transmitter of primary afferents in the nucleus of the solitary tract; (b) glutamatergic afferents may interact with gamma-aminobutyric acid system(s) in this region; (c) Gly also may participate in the mediation and/or modulation of cardiovascular or other visceral reflexes; and (d) amino acid neurotransmission may play an integral role in the neurogenic control of arterial pressure.

Amino Acids

Effects of stimulation of fastigial nucleus on cerebral blood flow in cats.

The goal of this study was to examine effects of electrical stimulation of the rostral fastigial nucleus on cerebral blood flow. Anesthetized cats were studied, and arterial pressure and blood gases were maintained at control levels during fastigial stimulation. In one group, we measured vessel diameter and velocity of blood flow through a pial artery with a Doppler probe and calculated blood flow as the product of cross-sectional area and velocity. Electrical stimulation of the fastigial nucleus produced a small increase in pial arterial flow of 16 +/- 6% (means +/- SE, P less than 0.05). Pial vascular resistance increased during moderate hypertension and decreased during decreases in arterial pressure, which indicates that cerebral vascular responses were not impaired. In a second group, cerebral blood flow was measured with microspheres. Blood flow to the pons and medulla increased 25 +/- 11 and 21 +/- 11%, respectively, during stimulation of the fastigial nucleus, but blood flow to the cerebral cortex did not increase significantly. Stimulation produced decreases in flow to the renal cortex and duodenum of 39 +/- 10 and 39 +/- 15%, respectively, and flow to the heart increased 48 +/- 22%, which indicates that the stimulus was efficacious. Thus electrical stimulation of the rostral fastigial nucleus in cats elicits only a small increase in cerebral blood flow.

Animals

A hyperthermic syndrome in two subjects with acute hydrocephalus.

Although intracranial hypertension may cause autonomic disturbances, as well as alterations in the regulation of body temperature, an acute hyperthermic syndrome with autonomic disturbance as a consequence of hydrocephalus has not been described previously. Two subjects presented with such a syndrome, with each of several episodes of acute shunt failure and hydrocephalus. With correction of the hydrocephalus, the autonomic disturbances and fever immediately cleared. Observations from human and experimental studies suggest some potential mechanisms for the development of the syndrome. One of the subjects of this report was being treated with neuroleptics at the time of hospitalization; in him, and potentially in other similar patients, the syndrome could easily be confused with the neuroleptic malignant syndrome. The need for prompt appreciation of the correct diagnosis was emphasized by the rapid clearing of all neurological signs after correction of the shunt malfunction in both of these patients.

Acute Disease

Glycine microinjected in the rat dorsal vagal nucleus increases arterial pressure.

Microinjections (25 nl) of glycine into the dorsal motor nucleus of the vagus in 21 rats elicited dose-dependent increases of arterial pressure and heart rate that were not seen with injections adjacent to the dorsal motor nucleus of the vagus. The responses to glycine were neurally mediated and could be blocked either by local pretreatment with strychnine or by combined vagotomy and ganglionic blockade. The data suggest that glycine receptors on, or in the region of, neurons of the dorsal motor nucleus of the vagus may have a role in the regulation of arterial pressure and heart rate.

Animals

Central modulation of gastric pressure by substance P: a comparison with glutamate and acetylcholine.

We have sought to determine if changes in arterial and gastric pressure occurred with selective chemical stimulation of the dorsomedial NTS. Substance P (SP) and L-glutamate (L-glu), but not acetylcholine (ACh), elicited a dose-dependent decrease in tonic gastric pressure and inhibited gastric phasic activity. As previously reported, L-glu and ACh, but not SP elicited dose-dependent arterial hypotension. The data support a putative role for SP in visceral reflexes mediated by vagal nerves.

Acetylcholine

Modulation of gastric and arterial pressure by nucleus tractus solitarius in rat.

By using L-glutamate as a physiological tool to selectively stimulate neurons in specific subnuclear regions of the nucleus tractus solitarius (NTS), we have sought to differentiate those regions that modulate cardiovascular activity from those that modulate gastric activity. Microinjections of L-glutamate (300 pmol/25 nl) into the dorsomedial NTS of alpha-chloralose-anesthetized rats elicited dose-dependent falls in arterial pressure (AP) of 37.5 +/- 7.7 Torr from a base line of 130 +/- 5.8 Torr and gastric pressure (GP) of 0.8 +/- 0.1 cmH2O and inhibited the usual 5-6 waves/min phasic activity. Microinjection into the ventromedial NTS did not affect AP but transiently lowered GP by 1.6 +/- 0.2 cmH2O and eliminated phasic waves. The GP changes were vagally mediated. Microinjections into the area postrema or the hypoglossal nucleus elicited neither AP nor GP changes. Microinjections in other NTS areas at the same rostral-caudal level did not alter GP consistently. This study suggests that local stimulation of neurons in a specific region of the NTS elicits vagally mediated alterations of tonic GP and phasic activity and that AP and GP can be influenced independently in the medial NTS region.

Animals