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.

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.

Projection sites of superficial and deep spinal dorsal horn cells in the nucleus tractus solitarii of the rat.

By using anterograde transport of biotin dextran amine injected into the cervical spinal dorsal horn, we have shown that fibres from superficial and deep dorsal horn project to the nucleus tractus solitarii via two distinct pathways. Afferent fibres from the superficial lamina (I-III) were found to course in the dorsal funiculus and terminate bilaterally in the caudal zone of the nucleus tractus solitarii (NTS), mainly within the commissural subnucleus. In contrast, afferents from the deeper dorsal horn laminae (IV-V) were found to course in the dorsolateral fasciculus and terminate ipsilaterally, mostly in the lateral areas of the caudal nucleus tractus solitarii. Similar, but more extensive patterns of labelled fibres were produced by injections into the white matter of the dorsal funiculus and dorsolateral fasciculus, respectively. These observations suggest that the caudal NTS not only serves as a location of visceral afferent convergence and integration, but may also be a receptive area for monosynaptic projections from dorsal horn neurons receiving sensory afferent inputs. Such projections may represent pathways through which NTS neurons are influenced by nociceptive and non-nociceptive information from the dorsal horn and thereby can co-ordinate the appropriate autonomic response, including adjustments in cardiorespiratory reflex output.

Immunohistochemical profiles of spinal lamina I neurones retrogradely labelled from the nucleus tractus solitarii in rat suggest excitatory projections.

Three morphologically distinct types of lamina I neurones, fusiform, flattened and pyramidal, project from the spinal cord to the caudal part of the nucleus tractus solitarii in the rat, and may represent a pathway whereby peripheral stimuli can modify autonomic functions. The neurochemistry of these three types of projection neurones was investigated using retrograde neuronal tracing with cholera toxin B-subunit combined with dual and triple immunofluorescence labelling for different neuroactive substances. None of the lamina I neurones with immunoreactivity for GABA or glycine were found to project to the nucleus tractus solitarii, whereas high levels of glutamate immunoreactivity, which may indicate a glutamatergic phenotype, were found in 18.4% of fusiform, 9.6% of pyramidal and 2.1% of flattened projection neurones. Immunoreactivity for calbindin-D28K was present in 34.9% of fusiform cells, 18.3% of pyramidal cells and 10.5% of flattened cells, and nitric oxide synthase immunoreactivity was detected in 13.8% of fusiform cells, 1.1% of pyramidal cells and 4.2% of flattened cells that had projections to the nucleus tractus solitarii. Calbindin immunoreactivity was co-localised in major subpopulations of projection neurones of each morphological type that contained glutamate immunoreactivity, whereas co-localisation of nitric oxide synthase immunoreactivity in these neurones was relatively uncommon. The pyramidal cell was the only retrogradely labelled cell type found to be immunoreactive for substance P, but few (<5%) of these neurones were immunolabelled. These data are consistent with the hypothesis that lamina I neurones projecting to the dorsal vagal complex are not inhibitory, and that some of them, belonging mostly to the fusiform and pyramidal types, may exert excitatory, glutamate- or substance P-mediated effects upon inhibitory interneurones in the nucleus tractus solitarii. Such excitatory pathways could be involved in the attenuation of the reflex control of blood pressure by both painful and innocuous peripheral stimuli, such as those arising in injury and exercise.

Gamma-aminobutyric acid receptor (GABA(A)) subunits in rat nucleus tractus solitarii (NTS) revealed by polymerase chain reaction (PCR) and immunohistochemistry.

Expression of mRNAs encoding seven GABA(A) receptor subunits (alpha1, alpha2, alpha3, alpha5, beta2, beta3, gamma2) in the nucleus tractus solitarii (NTS) of rat medulla oblongata was examined by reverse transcription-polymerase chain reaction (RT-PCR). All subunit mRNAs, except alpha5, were clearly detected. Band densities produced by alpha1, alpha3, beta3, and gamma2 subunits were greater than those corresponding to beta2 and alpha2 transcripts. The localization of these subunits in tissue sections through NTS was examined by immunohistochemistry. The differential patterns of immunoreactivity in neuronal somata and dendrites of NTS neurons were generally in agreement with the PCR results, confirming that mRNA expression is correlated with receptor protein synthesis. At ultrastructural level, alpha1, alpha3, beta2/3, and gamma2 subunits were localized in both cytoplasmic and subsynaptic sites, the latter often apposed to GABA immunoreactive synapses. These results suggest that ionotropic receptors comprising the alpha1, alpha3, beta2/3, and gamma2 may mediate inhibitory GABA responses in the NTS.

Nitric oxide producing neurones in the rat medulla oblongata that project to nucleus tractus solitarii.

The production of nitric oxide in neurones of the rat medulla oblongata that project to the nucleus tractus solitarii (NTS) was examined by simultaneous immunohistochemical detection of nitric oxide synthase (NOS) and of cholera toxin B-subunit (CTb), which was injected into the caudal zone of the NTS. Neurones immunoreactive for CTb and neurones immunoreactive for NOS were widely co-distributed and found in almost all the anatomical divisions of the medulla. Dual-labelled cells, containing both CTb and NOS immunoreactivities were more numerous ipsilaterally to the injection sites. They were concentrated principally in the more rostral zone of the NTS, raphé nuclei, dorsal, intermediate and lateral reticular areas, spinal trigeminal and paratrigeminal nuclei and the external cuneate and medial vestibular nuclei. Isolated dual-labelled neurones were also scattered throughout most of the divisions of the reticular formation. These observations indicate that many areas of the medulla that are known to relay somatosensory and viscerosensory inputs contain NOS immunoreactive neurones that project to the NTS, and may, therefore, contribute to the dense NOS-immunoreactive innervation of the NTS. The release of nitric oxide from the axon terminals of these neurones may modulate autonomic responses generated by NTS neurones in relation to peripheral sensory stimuli, and thus ultimately regulate sympathetic and/or parasympathetic outflow.

Glycine-immunoreactive synaptic terminals in the nucleus tractus solitarii of the cat: ultrastructure and relationship to GABA-immunoreactive terminals.

Postembedding immunogold labeling methods applied to ultrathin and semithin sections of cat dorsomedial medulla showed that neuronal perikarya, dendrites, myelinated and nonmyelinated axons, and axon terminals in the nucleus tractus solitarii contain glycine immunoreactivity. Light microscopic observations on semithin sections revealed that these immunoreactive structures were unevenly distributed throughout the entire nucleus. At the electron microscopic level, synaptic terminals with high levels of glycine-immunoreactivity, assumed to represent those releasing glycine as a neurotransmitter, were discriminated from terminals containing low, probably metabolic levels of glycine-immunoreactivity, by a quantitative analysis method. This compared the immunolabeling of randomly sampled terminals with a reference level of labeling derived from sampling the perikarya of dorsal vagal neurones. The vast majority of these "glycinergic" terminals contained pleomorphic vesicles, formed symmetrical synaptic active zones, and targeted dendrites. They appeared to be more numerous in areas of the nucleus tractus solitarii adjoining the tractus solitarius, but rather scarce caudally, medially, ventrally, and in the dorsal motor vagal nucleus. In a random analysis of the entire nucleus tractus solitarii, 26.2% of sampled terminals were found to qualify as glycine-immunoreactive. In contrast, boutons immunoreactive for gamma-aminobutyric acid (GABA) were more evenly distributed throughout the dorsal vagal complex and accounted for 33.7% of the synaptic terminals sampled. A comparison of serial ultrathin sections suggested three subpopulations of synaptic terminals: one containing high levels of both GABA- and glycine-immunoreactivities (21% of all terminals sampled), one containing only GABA-immunoreactivity (12.7%), and relatively few terminals (5.2%) that were immunoreactive for glycine alone. These results were confirmed by dual labeling of sections using gold particles of different sizes. This study reports the first analysis of the ultrastructure of glycinergic nerve terminals in the cat dorsal vagal complex, and the pattern of coexistence of glycine and GABA observed provides an anatomical explanation for our previously reported inhibitory effects of glycine and GABA on neurones with cardiovascular and respiratory functions in the nucleus tractus solitarii.

Labelling of rat vagal preganglionic neurones by carbocyanine dye DiI applied to the heart.

We describe a method for applying the carbocyanine dye DiI to the rat heart that takes advantage of the dye's lipophilic properties and its ability to diffuse easily into tissues, and results in specific retrograde labelling of cardiac vagal preganglionic neurones in the medulla oblongata. Most of the labelled neurones were found bilaterally in the nucleus ambiguus (81%), with a few sparsely distributed in the dorsal motor vagal nucleus (6.5%), and in an intermediate area located between these two nuclei (12.5%). We contend that the method of applying DiI crystals to the surface of the heart is a more efficient, accurate and reproducible method of retrograde labelling than the injection of tracers into this very delicate tissue.

Co-localization of c-Fos and neurotransmitter immunoreactivities in the cat brain stem after carotid sinus nerve stimulation.

To reveal neurones in the cat medulla oblongata involved in carotid baroreceptor/chemoreceptor reflexes, the distribution of c-Fos oncoprotein immunoreactivity was studied following electrical stimulation of the right carotid sinus nerve. The neurochemistry of the activated neurones was investigated using antisera to tyrosine hydroxylase, neuropeptide Y, somatostatin, and glutamate. Nitric oxide containing neurones were identified using antiserum to nitric oxide synthase (NOS) and by the histochemical localization of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase. Following sinus nerve stimulation numerous c-Fos-IR cells were detected both ipsilaterally and contralaterally in the nucleus tractus solitarii, the area postrema and throughout the ventrolateral medulla. Dual labelling studies revealed that 3.3% of c-Fos-immunoreactive cells in the nucleus tractus solitarii were also immunoreactive for tyrosine hydroxylase. The double labelled cells were scattered within the medial and ventrolateral subnuclei, predominantly rostral to obex. A higher proportion (10.3%) of c-Fos-IR cells in the ventrolateral medulla also showed tyrosine hydroxylase immunoreactivity. Caudal to obex, these were scattered in the reticular formation between the spinal trigeminal nucleus and the lateral reticular nucleus, while more rostrally they were found within the lateral reticular nucleus, the nucleus ambiguus and the lateral tegmental field. Cells expressing c-fos and reactive for glutamate, neuropeptide Y or NADPH-diaphorase (or NOS) were only rarely seen, and co-localization of c-Fos and somatostatin immunoreactivities was not seen. These results suggest that of the neurones forming pathways within the medulla activated on carotid sinus nerve stimulation, presumably mediating baro- and chemoreceptor reflexes, relatively few utilize catecholamines, glutamate, neuropeptide Y or nitric oxide as their transmitter substance.

Influence of peripheral targets on the expression of calcitonin gene-related peptide immunoreactivity in rat cranial motoneurones.

Calcitonin gene-related peptide-like immunoreactivity (CGRP-ir) is displayed by motoneurons that innervate striated muscle but is absent from preganglionic parasympathetic motoneurons. One hypothesis to explain this is that CGRP gene expression in motoneurons is, in part, dependent on influences from the innervated organ. To test this hypothesis, we cross-anastomosed the right hypoglossal and cervical vagal nerves of rats so that the vagal motoneurons grew to innervate the musculature of the tongue. Following a recovery period of 17 to 52 weeks, the distribution of CGRP-ir in the dorsal motor vagal nucleus was determined in both cross-anastomosed animals and self-anastomosed control animals. Successful reinnervation of the tongue musculature by vagal motoneurons was demonstrated by showing that electrical stimulation of the central vagus/peripheral hypoglossal nerve produced a twitch of the tongue muscles. Motoneurones of the dorsal motor vagal nucleus, which now innervated the tongue were found to express CGRP-ir, which was evident from the double labeling of neurons with both horseradish peroxidase and CGRP-ir. Motoneurones of the dorsal motor vagal nucleus contralateral to the cross-anastomosis remained CGRP negative. Similarly, motoneurons of the dorsal motor vagal nucleus in control animals where the vagus nerve was self-anastomosed remained CGRP negative, showing that an induction of CGRP expression is not a result of nerve section itself. We suggest that a signal from the striated muscle transported retrogradely via the motor axon regulates expression of CGRP-ir in motoneurons.

Glutamate-immunoreactivity in identified vagal afferent terminals of the cat: a study combining horseradish peroxidase tracing and postembedding electron microscopic immunogold staining.

Using electron microscopic immunohistochemistry we have shown that strong glutamate-immunoreactivity (glutamate-ir) is present in neuronal cell bodies of the nodose ganglion, axons in the tractus solitarius and afferent terminals in the nucleus tractus solitarii. Vagal afferent fibres were specifically labelled by transganglionic retrograde transport of horseradish peroxidase (HRP). Fifty-seven per cent of the HRP-labelled terminals in the dorsomedial medulla were found to contain a high level of glutamate-ir, suggesting that a population of vagal afferent fibres uses glutamate as a neurotransmitter substance. There were no apparent ultrastructural differences between glutamate-ir and non-glutamate-ir vagal afferent terminals, both classes mainly containing rounded vesicles and forming asymmetric synapses. However, some difference in their preference for postsynaptic target was noted. The great majority (83%) of non-glutamate-ir vagal afferent terminals made axodendritic synapses, but only just over half (57%) of the glutamate-ir vagal terminals made synaptic contact with dendrites. Approximately 13% of the HRP-labelled terminals were found to make synaptic contact with HRP-labelled dendrites or soma of motoneurones of the dorsal vagal motor nucleus, confirming the existence of monosynaptic connections between vagal afferent fibres and vagal motoneurones.

Co-localization of neurotransmitter immunoreactivities in putative nitric oxide synthesizing neurones of the cat brain stem.

The distribution of nitric oxide producing neurones in the medulla oblongata of the cat was investigated using nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, and nitric oxide synthase (NOS) immunohistochemistry. The pattern of staining obtained with both methods was found to be similar. Strongly diaphorase and NOS reactive neurones were present in the paramedian and lateral tegmental fields, including the regions occupied by the A1/C1 catecholamine cell groups, the nucleus ambiguus and lateral reticular nucleus, and in a number of sensory nuclei including the nucleus of the tractus solitarius and the dorsal column nuclei. The extent of co-localization of NADPH-diaphorase with a number of neuropeptides and neurotransmitters was investigated by combining NADPH-diaphorase histochemistry with immunocytochemistry for neuropeptide Y, somatostatin, glutamate, cholecystokinin and tyrosine hydroxylase. NADPH-diaphorase reaction product was observed in neurones immunoreactive for glutamate and somatostatin. These double-labelled cells were found in the paramedian region, lateral reticular field, the nucleus prepositus hypoglossi and in the rostral nucleus of the tractus solitarius. In the rostral ventrolateral medulla NADPH-diaphorase/somatostatin immunoreactive cells were found in the paragigantocellular nucleus. NADPH-diaphorase/glutamate immunoreactive cells overlapped the nucleus ambiguus, the lateral reticular nucleus and the A1/C1 catecholaminergic cell groups. In addition, a few NADPH-diaphorase/glutamate immunoreactive cells were found in the paraolivary area and gigantocellular tegmental field, in the external cuneate and infratrigeminal nuclei. The functional implications of the co-localization of nitric oxide with these neurotransmitters in areas of the medulla concerned with cardiovascular regulation is discussed.

Glutamate, gamma-aminobutyric acid and tachykinin-immunoreactive synapses in the cat nucleus tractus solitarii.

Neurophysiological and pharmacological evidence suggests that glutamate, gamma-aminobutyric acid and tachykinins (substance P and neurokinin A) each have a role in cardiovascular regulation in the nucleus tractus solitarii. This study describes the ultrastructural relationships between nerve terminals immunoreactive for these substances in the nucleus tractus solitarii of the cat using post-embedding immunogold (single and double) labelling techniques on sections of tissue embedded in LR White resin. The technique combines a high specificity of labelling with good ultrastructural and antigenic preservation. Glutamate-immunoreactive terminals, recognized by their high density of gold particle labelling compared to the mean tissue level of labelling, accounted for about 40% of all synaptic terminals in the region of the nucleus tractus solitarii analysed (medial, dorsal, interstitial, gelatinosus and dorsolateral subnuclei). They appeared to comprise several morphological types, but formed mainly asymmetrical synapses, most often with dendrites of varying size, and contained spherical clear vesicles together with fewer dense-cored vesicles. Substance P- and neurokinin A-immunoreactive terminals were fewer in number (9% of all terminals) but similar in appearance, with the immunoreaction restricted to the dense-cored vesicles. Analysis of serial- and double-labelled sections showed a co-existence of substance P and neurokinin A-immunoreactivity in 21% of glutamate-immunoreactive terminals. Immunoreactivity for gamma-aminobutyric acid was found in 33% of all terminals in the nucleus tractus solitarii. These predominantly contained pleomorphic vesicles and formed symmetrical synapses on dendrites and somata. Possible sites of axo-axonic contact by gamma-aminobutyric acid-immunoreactive terminals onto glutamate-or tachykinin-immunoreactive terminals were rare, but examples of adjacent glutamate and gamma-aminobutyric acid-immunoreactive terminals synapsing on the same dendritic profile were frequent. These results provide an anatomical basis for a gamma-aminobutyric acid mediated inhibition of glutamatergic excitatory inputs to the nucleus tractus solitarii at a post-synaptic level.

Electrical stimulation of the vagus increases extracellular glutamate recovered from the nucleus tractus solitarii of the cat by in vivo microdialysis.

Release of glutamate into the extracellular space of the cat nucleus tractus solitarii (NTS) was measured by in vivo microdialysis and high performance liquid chromatography. Perfusion of the probe with 100 mM potassium increased glutamate release by 211% (P < 0.001), while electrical stimulation of the cervical vagus increased release by 53% (P < 0.01). These results are compatible with the hypothesis that glutamate is a neurotransmitter released by vagal afferent nerve terminals in the NTS.

Distribution of dopamine-containing neurons and fibres in the feline medulla oblongata: a comparative study using catecholamine-synthesizing enzyme and dopamine immunohistochemistry.

The distribution of dopamine-immunoreactive neurons and fibres in the feline medulla oblongata was examined by immunocytochemistry with antisera to the catecholamine-synthesizing enzymes tyrosine hydroxylase, dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase, and with antisera to the catecholamines dopamine and L-dihydroxyphenylalanine. Neurons immunoreactive for the catecholamine-synthesizing enzymes were found in two regions of the medulla, the ventrolateral A1 region and the dorsomedial A2 region. Double-staining studies with antisera to the enzymes indicated that a population of neurons within both regions were immunoreactive for tyrosine hydroxylase but not dopamine-beta-hydroxylase or phenylethanolamine-N-methyltransferase, implying that they synthesize dopamine. Studies using the dopamine antisera demonstrated the presence of dopamine-immunoreactive neurons in both the ventrolateral and dorsomedial regions of the medulla; in the dorsomedial region, they were found in the area postrema, nucleus tractus solitarius and dorsal motor vagal nucleus, mainly at levels caudal to the obex. Dopamine-immunoreactive fibres were found in several areas of the medulla including the nucleus tractus solitarius, inferior olive, dorsal motor vagal, spinal trigeminal, hypoglossal, cuneate, gracile, and raphe nuclei. Double-staining studies with antisera to dopamine and dopamine-beta-hydroxylase revealed a population of cells immunoreactive for dopamine alone. The presence of some double-stained neurons, however, implies some cross-reactivity of the dopamine antiserum with noradrenaline or adrenaline and/or recognition of dopamine present as a metabolic intermediary in some noradrenergic neurons. No L-dihydroxyphenylalanine-immunoreactive neurons were found in the medulla, although fibres were seen. These data provide evidence for the existence of catecholamine neurons which utilize dopamine as a final synthetic product within the medulla oblongata.

Sequential in vivo measurements of body composition of calves exposed to natural infection with gastrointestinal nematodes.

Sequential in vivo measurements of total body water, exchangeable sodium and exchangeable potassium, made by radioisotopic dilution techniques, were used to determine changes in body composition in calves exposed to natural infections with gastrointestinal nematodes during their first grazing season. Two groups of calves were studied, one of which received a sustained release anthelmintic bolus at turn out. Over the grazing season the bolus-treated calves showed a significantly improved pattern of bodyweight gain, compared with the untreated control calves. There were also significant increases in both total body water and exchangeable potassium, as a percentage of the bodyweight, in the bolus calves compared with the controls. These findings indicated that body protein as a percentage of bodyweight was increased in the bolus animals. The bolus-treated calves also had significantly lower serum pepsinogen concentrations, faecal egg counts and worm burdens.

Changes in R-R interval at the start of muscle contraction in the decerebrate cat.

1. The effect on R-R interval of a brief hindlimb contraction, elicited by electrical stimulation of L7 ventral roots, was investigated in decerebrate cats. The first series of experiments was performed at both low and high carotid sinus pressure to vary the level of vagal tone. When carotid sinus pressure was elevated to increase vagal tone, contraction commenced 1 s later. 2. The change in R-R interval at low carotid sinus pressure was expressed as the difference between the mean of the five R-R intervals immediately preceding contraction and the mean of the last five R-R intervals at the end of a 5 s contraction. At high carotid sinus pressure, the change was expressed as the difference between the mean of the last five R-R intervals at the end of a 5 s contraction and the mean of five R-R intervals at an equivalent time after raising pressure alone. 3. Hindlimb contraction at low carotid sinus pressure produced a significant reduction in R-R interval from 359 +/- 25 (mean +/- S.E.M. n = 8) to 336 +/- 24 ms (P less than 0.005). At high carotid sinus pressure the response was enhanced with contraction producing a reduction in R-R interval from 474 +/- 45 to 419 +/- 47 ms (P less than 0.001). 4. The shortening of R-R interval produced by hindlimb contraction at high carotid sinus pressure, 55 +/- 8 ms, was significantly greater than that observed at low sinus pressure, 23 +/- 5 ms (P less than 0.001, n = 8, paired t test). This pattern of response was also seen at stimulation frequencies as low as 10 Hz. 5. In a second series of experiments, designed to determine the latency of the cardiac acceleration, the minimum latency between the onset of L7 ventral root stimulation and the end of the first shortened R-R interval was 687 +/- 29 ms (n = 5). 6. Atropine (0.4 mg kg-1, I.V.) prevented a 5 s contraction from producing any change in R-R interval. 7. These results indicate that afferent information originating from receptors in contracting muscles is responsible for producing an immediate shortening of R-R interval, which is mediated by vagal withdrawal. The possibility that the shortening of R-R interval at the start of contraction is linked to a reduction in arterial baroreceptor reflex sensitivity, possibly via inhibitory effects on neurones forming the central pathway of the baroreceptor reflex, is discussed.

Effect of sustained release and pulse release anthelmintic intraruminal devices on development of pathophysiological changes and parasite populations in calves infected with Ostertagia ostertagi and Cooperia oncophora.

An experiment was conducted in calves to investigate the effect of sustained release and pulse release anthelmintic intraruminal boli on the development of pathophysiological changes following daily infection with Ostertagia ostertagi and Cooperia oncophora for six weeks. After infection various pathophysiological changes were detected including increases in serum pepsinogen concentration, enteric plasma protein losses and in the catabolic rate of albumin. Such changes developed rapidly in the unprotected calves following patency after 17 days and persisted until the termination of the study. There were indications that the sustained anthelmintic release device was more efficacious than the pulse anthelmintic release device in reducing the worm burdens and early pathophysiological changes associated with infection. It was found at necropsy that the release of anthelmintic by the oxfendazole pulse release bolus had been delayed in several calves.

Changes in the baroreceptor reflex at the start of muscle contraction in the decerebrate cat.

1. The action of muscle contraction on the sensitivity of the cardiac vagal component of the baroreceptor reflex was examined in decerebrate cats. 2. The sensitivity of the baroreceptor reflex was expressed as the difference between the maximum prolongation of the R-R interval in response to carotid sinus baroreceptor stimulation and the mean of ten R-R intervals immediately before carotid sinus pressure elevation. 3. Muscle contraction elicited by electrical stimulation of L7 ventral roots (50 Hz) significantly reduced the sensitivity of the baroreceptor reflex by reducing the prolongation of the R-R interval from 269 +/- 31 to 159 +/- 22 ms. 4. Inhibition of the cardiac vagal component of the baroreceptor reflex was seen just 1 s after the onset of contraction and with stimulation frequencies as low as 10 Hz. 5. These results show for the first time that changes in the sensitivity of the baroreceptor reflex during exercise result in part from afferent information originating in the contracting muscles.