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Biomedical subjects

K M Spyer

Publications and source records attributed to K M Spyer.

At least 91 records · Page 5Linked to original sources
PubMed1990

Nucleus tractus solitarius as mediator of evoked parabrachial cardiovascular responses in the decerebrate rabbit.

1. The present study has assessed the importance of neurones within the nucleus tractus solitarius (NTS) in mediating the cardiovascular response evoked from the parabrachial nucleus (PBN) in the decerebrate rabbit. Microinjection techniques were employed so that the magnitude of the circulatory responses elicited from the PBN could be compared before, and after, kainic acid or bicuculline were microinjected into restricted regions of the NTS. 2. Electrical stimulation of the PBN (both medial and lateral regions) evoked variable changes in heart rate, a pressor response, vasoconstriction in the hindlimb and an increase in renal sympathetic nerve activity. Glutamate injected into these regions of the PBN elicited a similar pattern of response except that a tachycardia was observed consistently. 3. Both electrical and chemical stimulation of restricted regions of the NTS evoked bradycardia and a depressor response together with an increase in femoral vascular conductance and an inhibition of activity in the renal nerve. 4. Chemical lesions placed in these regions of the NTS by microinjecting kainic acid were found to attenuate both the heart rate and arterial blood pressure responses elicited from sites in the medial and lateral PBN using either electrical or chemical stimulation. Equivalent effects were produced on microinjecting the GABAa receptor antagonist bicuculline into the NTS. 5. These data indicate that NTS neurones play a part in mediating the cardiovascular responses that are evoked from the PBN and suggest that the action of the PBN at the level of the NTS is mediated via a GABAergic mechanism.

Animals↗
PubMed1989

Investigation of inositol hexakisphosphate actions in rat nucleus tractus solitarius in vitro.

Intracellular recordings from neurones in slices of rat brainstem containing the nucleus tractus solitarius were made to examine the effects of inositol hexakisphosphate (IP6) in a region where cardio-depressant effects had been reported in vivo in the same species. Bath application of IP6 failed to consistently alter the excitability, membrane potential or resistance even at concentrations up to 44 microM. Glutamate application (1-1.5 mM) was, however, effective in increasing excitability and depolarising these neurons. Thus, the neuronal mechanisms underlying the cardiovascular effects reported in vivo have not been resolved.

Animals↗
PubMed1989

Interactive responses to stimulation of the amygdaloid central nucleus and baroreceptor afferent activation in the rabbit.

Recent evidence suggests that the amygdaloid central nucleus (ACE) may contribute to the regulation of arterial baroreceptor-vagal reflex sensitivity. To obtain additional data relevant to this suggestion, interactions between stimulation of the ACE and arterial baroreceptor afferent activation were examined. New Zealand rabbits were anesthetized with alpha-chloralose and a stimulating electrode was implanted stereotaxically in the ACE. In the first series of experiments, cardiovascular responses to stimulation of the ACE were assessed during periods in which blood pressure was decreased using sodium nitroprusside or increased in the rostral arterial compartment by inflating the tip of a Swan-Ganz catheter positioned in the descending aorta. It was found that the magnitude of bradycardia to stimulation of the ACE was correlated with the level of arterial blood pressure at the onset of stimulation, such that higher blood pressures were associated with larger bradycardic responses. These data suggest that arterial baroreceptor afferent activity may be an important factor in the elicitation of bradycardia from the ACE. In the second series of experiments, the aortic nerve was isolated, and cardiovascular responses to stimulation of the aortic nerve and to low frequency (5 Hz) stimulation of the ACE were assessed both alone and in combination. Stimulation of the aortic nerve during low frequency stimulation of the ACE was found to produce bradycardia of a significantly larger magnitude than the sum of the responses produced by each stimulus presented alone. These data demonstrate that bradycardia to stimulation of baroreceptor afferent fibers is augmented significantly during low frequency stimulation of the ACE. Taken together, these results are consistent with the notion that the ACE may contribute to the sensitivity of the arterial baroreceptor-vagal reflex.

Afferent Pathways↗
PubMed1989

Neural mechanisms involved in cardiovascular control during affective behaviour.

The changes in respiration and cardiovascular output seen during mammalian defensive behaviour are no longer considered to be the product of simple reflexes. Nuclei in the diencephalon (in particular, in the hypothalamus and amygdala) are involved in controlling defence reactions. In this article, K. M. Spyer describes the evidence illustrating the actions of these descending influences and discusses the potential for future modelling paradigms in relation to cardiovascular control.

Animals↗
PubMed1988

Opiate receptor subtypes in the nucleus tractus solitarii of the cat: the effect of vagal section.

The distribution of mu, delta and kappa opioid receptors in the lower brainstem of the cat has been determined autoradiographically by studying the binding of tritiated [D-Ala2,MePhe4,Glyol5][tyrosyl-3,5-3H]enkephalin (DAGO), [D-Pen2,D-Pen5][tyrosyl-3,5-(n)-3H]enkephalin (DPDPE) and [9-3H]ethylketazocine (EKC), respectively. General opiate receptor binding was established using [3H]naloxone (NX). High densities of [3H]NX and DAGO binding sites were found most prominently in the nucleus tractus solitarii. There was no DPDPE and very weak EKC binding within this nucleus, although both these ligands bound to the cerebellum. The effect of unilateral vagotomy on receptor density was examined. Sectioning the cervical vagus had no effect on the density of mu receptors in the brainstem. Sectioning the vagus, accompanied by nodose ganglion excision, led to a marked depletion of mu receptors which was restricted to dorsal and medial regions of the ipsilateral nucleus tractus solitarii at, and rostral to, the obex. These results suggest that mu opiate receptors are located presynaptically on vagal afferents terminating within a restricted region of the nucleus tractus solitarii.

Animals↗
PubMed1988

Intracellular analysis of respiratory-modulated hypoglossal motoneurons in the cat.

Intracellular recordings from hypoglossal motoneurons in the brainstem of cats are described, along with postsynaptic potentials evoked by superior laryngeal, vagal and carotid sinus nerve stimulation. The study concentrates on hypoglossal motoneurons with respiratory-related discharge, which can be categorized into inspiratory, inspiratory/early-expiratory and expiratory patterns. Seven cells were labelled with horseradish peroxidase, their location and morphology are described. Stimulation of laryngeal receptors by balloon inflation or by water injection into the larynx, or mimicked by electrical stimulation of the superior laryngeal nerve results in enhanced postinspiratory activity in those cells (inspiratory/early-expiratory, expiratory) already receiving postinspiratory excitation; or actually produces a wave of postinspiratory depolarization in cells (inspiratory) previously quiescent during that period. It is concluded that the firing pattern of the respiratory-modulated hypoglossal motoneurons is unlikely to be static but depends on other factors, one of these being the level of ongoing, or previous laryngeal receptor stimulation.

Action Potentials↗
PubMed1988

The brain stem localization of vagal preganglionic neurones in the ferret, Mustela putorius furo.

Horseradish peroxidase-wheatgerm agglutinin was injected into the cervical vagus nerve of adult ferrets. Efferent fibres coursing in the vagus nerve were shown to originate in the dorsal vagal motor nucleus (DmnX), the nucleus ambiguus (nA), a region ventral to the nucleus ambiguus (VnA) and the reticular formation between DmnX and nA. The distribution of vagal preganglionic neurones in the ferret is compared with data already obtained in similar studies conducted in other mammals.

Animals↗
PubMed1988

Baroreceptor inputs to the nucleus tractus solitarius in the cat: postsynaptic actions and the influence of respiration.

1. The postsynaptic action of carotid sinus nerve (SN), aortic nerve (AN), superior laryngeal nerve (SLN) and vagal nerve (VN) stimulation has been studied on neurones in the nucleus of the tractus solitarius (NTS) in vivo. 2. Three distinct patterns of postsynaptic responses were evoked by SN stimulation, an EPSP, an EPSP-IPSP sequence and an IPSP, observed separately in individual neurones. This diversity of response was represented in cells proven to receive baroreceptor input by inflation of a balloon-tipped catheter within the ipsilateral carotid sinus. 3. Virtually none of the neurones identified as baroreceptive exhibited pulse-related discharge. 4. A variety of influences to AN, SLN and VN stimulation were observed in neurones receiving baroreceptor afferent information. This wide convergence of input implies that this region of the brain stem is important in the integration of cardiovascular reflexes. 5. The hypothesis was tested that respiratory 'gating' of the baroreceptor reflex is produced by synaptic actions within the NTS. There was an absence of any modification of PSPs by lung inflation and by variations in the timing of the stimulation of the afferent nerves within the respiratory cycle. These observations indicate that respiratory modifications of the baroreceptor reflex must occur at later stages in the reflex pathway.

Action Potentials↗
PubMed1988

Baroreceptor inputs to the nucleus tractus solitarius in the cat: modulation by the hypothalamus.

1. The effects of stimulation within the hypothalamic defence area (HDA) on the activity of neurones in the nucleus of the solitary tract (NTS) have been investigated in vivo. 2. HDA stimulation exerted marked influences on NTS neurones. Approximately two-thirds of units receiving a carotid sinus nerve (SN) input were inhibited by HDA stimulation. All units shown to receive an excitatory input from carotid sinus baroreceptors were inhibited by HDA stimulation. 3. The specificity of the HDA stimulation was investigated by generalized hypothalamic stimulation. In these experiments the number of units activated by SN stimulation that were inhibited was reduced considerably. A much smaller percentage (27%) of baroreceptive units were inhibited from hypothalamic stimulation outside the defence area. 4. Intracellular recordings revealed that HDA stimulation evoked a long-lasting hyperpolarization of membrane potential that resulted from postsynaptic inhibition (rather than disfacilitation). The HDA-evoked IPSP 'shunted' the SN-evoked EPSP when the SN stimulus was timed to occur during the initial peak hyperpolarizing phase of the HDA-evoked IPSP. 5. HDA stimulation disinhibited cells receiving an inhibitory input from the carotid sinus baroreceptors. 6. The effects of HDA stimulation were not limited to cells receiving SN afferent information or to cells within the NTS. 7. Our results explain, at the intracellular level, the mechanism for the central suppression of the baroreceptor reflex that forms an integral part of the defence response in the cat.

Action Potentials↗
PubMed1988

Hypothalamic inhibition of neurones in the nucleus tractus solitarius of the cat is GABA mediated.

1. In pentobarbitone-anaesthetized cats extracellular activity of neurones in the vicinity of the nucleus tractus solitarius receiving inputs from the carotid sinus nerve (SN) and/or vagus nerve (VN) during stimulation of the hypothalamic defence area (HDA) and application of gamma-aminobutyric acid (GABA) and glycine and their antagonists have been studied. 2. A total of forty neurones have been tested, of which twenty-four only had an input from the SN, one only from the VN, twelve from both nerves and three had neither SN or VN inputs. 3. Short trains of stimuli to the HDA inhibited both the ongoing activity (if present) and evoked discharge in thirty-nine of the forty neurones tested. 4. In the forty cells tested ionophoretic application of GABA reduced (4) or totally inhibited (35) neuronal discharge whilst in the thirty-eight tested with glycine discharge was totally (25) or partially (12) suppressed. 5. Ionophoresis of bicuculline totally (14) or partially (6) antagonized the inhibitory actions of GABA in the twenty-five cells tested, and in eighteen of these the ongoing and/or evoked activity was simultaneously increased. In eighteen of the nineteen cells tested this level of bicuculline also antagonized the inhibitory actions of HDA stimuli whereas in none of the sixteen cells tested did it affect glycine-evoked inhibitions. 6. Ionophoretic application of strychnine antagonized the inhibitory effects of glycine in eight of nine cells tested but in these eight cells strychnine had no effect on ongoing or evoked discharges, GABA- or HDA-evoked inhibitions. 7. In a chloralose-anaesthetized cat five neurones receiving SN inputs (three also receiving VN inputs) were recorded. All could be inhibited by HDA stimuli and by application of GABA. In the three of four cells in which bicuculline antagonized GABA inhibitions, the effects of HDA stimuli were simultaneously antagonized whereas glycine-evoked inhibitions were unaffected. 8. In two neurones, in addition to inhibiting neuronal discharge HDA stimulation also evoked activity in the cells. In a further four neurones similar excitatory responses were uncovered when the HDA inhibitory effects were antagonized by bicuculline. 9. The importance of these observations in cardiovascular control and in the functioning of the baroreceptor reflex is discussed.

Action Potentials↗
PubMed1988

Synaptic rhythm of caudal medullary expiratory neurones during stimulation of the hypothalamic defence area of the cat.

1. Intracellular recordings were made from caudal medullary expiratory neurones in anaesthetized, paralysed, artificially ventilated and vagotomized cats before during and after the tachypnoeic response evoked by stimulation of the perifornical region of the hypothalamus. 2. The tachypnoeic response was evoked in seven of ten cats tested, and was represented in the phrenic nerve by a rapid two- to threefold increase in the frequency of the respiratory rhythm. The shortened duration of inspiratory discharge in the phrenic nerve was accompanied by an increase in its rate of development. If initially present, post-inspiratory phrenic discharge was intensified and extended throughout the shortened expiratory interval. 3. Intracellular recordings were obtained from twenty-one expiratory neurones during intermittent hypothalamic stimulation with short trains of pulses. Eighteen neurones showed a regular, short-latency sequence of synaptic events which consisted of an initial depolarizing potential (presumed EPSP) and a following hyperpolarizing potential (Cl--mediated IPSP) of long duration (50-150 ms when measured in expiration). The IPSP was accompanied by a phasic cessation of phrenic nerve discharge of comparable duration which was succeeded by intensified discharge. In three neurones (one experiment) the IPSP response was absent. 4. Sixteen neurones showing the EPSP-IPSP sequence were held for sufficiently long to record changes in the respiratory-related membrane potential pattern accompanying stimulation. The reduced expiratory time accompanying the response resulted in a shortened expiratory burst. In four neurones showing evidence of IPSPs in early expiration (post-inspiratory IPSPs), stimulation resulted in a phasic weakening of this inhibition which resulted in a more rapid approach to threshold and a steady rather than delayed increase in discharge. A low level of post-inspiratory IPSPs extended throughout most of the shortened expiration, resulting in an alternating rhythm of inspiratory and post-inspiratory inhibition. In the twelve neurones lacking such post-inspiratory IPSPs stimulation had no obvious effect on the shape of the expiratory trajectory. 5. In neurones which received an IPSP from hypothalamic stimulation, the overall response was associated with reduced amplitude and increased rate of decline of inspiratory inhibition of expiratory neurones. Three neurones showed high-frequency (70-80 Hz) oscillation of the membrane potential during inspiration (Mitchell & Herbert, 1974b). Hypothalamic stimulation resulted in a transient suppression of this oscillation. 6. We conclude that the short-latency inhibitory component of the response to hypothalamic stimulation is widely distributed, including expiratory neurones, some fraction of the inspiratory population and the neurones responsible for inspiratory and post-inspiratory inhibition.

Animals↗
PubMed1987

Central respiratory drive-related activity in sympathetic nerves of the rat: the regional differences.

In halothane-anaesthetized, vagotomized, SA-denervated rats, the activity of various sympathetic nerves has been analyzed with respect to phrenic nerve discharge (an indicator of central respiratory drive (CRD)). The cervical and lumbar sympathetic nerves had maximal activity following, and were least active during phrenic nerve discharge. In contrast, the splanchnic, cardiac, renal and adrenal nerves exhibited their activity peak during phrenic nerve discharge (i.e. inspiration). Similar activity profiles were observed after ganglion blockade in the mixed pre- and postganglionic fibre preparations. These observations indicate that it is the subpopulations of preganglionic neurones and the proportional contribution of each to whole-nerve activity which give rise to the differences in CRD-related activity profiles between nerves.

Action Potentials↗
PubMed1987

The cardiovascular responses elicited from the posterior cerebellar cortex in the anaesthetized and decerebrate rabbit.

1. In this study the posterior cerebellar cortex has been electrically stimulated and changes in heart rate, arterial blood pressure, regional blood flows and renal sympathetic nerve discharge have been recorded in both the anaesthetized and the decerebrate unanaesthetized rabbit. 2. Specifically, lobules VII, VIII, IX and X of the posterior cerebellar vermis were stimulated but the only region which elicited cardiovascular changes was lobule IX (the uvula). The responsive area of the uvula was localized to the medial regions of sublobules a, b and c and was identical in both anaesthetized and decerebrate animals. 3. Under urethane anaesthesia, uvula stimulation evoked a small bradycardia, a fall in arterial pressure, a transient inhibition of renal sympathetic nerve activity, with no change in renal vascular conductance, and an increase in femoral vascular conductance. 4. Stimulation of an identical area in the decerebrate rabbit evoked a marked tachycardia, an increase in blood pressure, maintained increase in renal sympathetic nerve discharge, and decreases in both renal and femoral conductances. 5. The response evoked from the decerebrate rabbit could be reversed by a small dose of anaesthetic to a pattern of response which was essentially identical to that seen in the urethane-anaesthetized rabbit. 6. This influence of anaesthetics on the pattern of cardiovascular responses that may be elicited from the cerebellar cortex indicates that caution should be exercised when making physiological inferences on the basis of stimulation experiments in anaesthetized preparations. 7. In the light of the cardiovascular changes that may be evoked from the uvula, and recent neuroanatomical and neurophysiological data concerning afferent and efferent connexions of this cerebellar region, we discuss the possibility that the uvula plays a role in the alerting reaction of the rabbit.

Anesthesia, General↗
PubMed1987

Cardiovascular and phrenic nerve responses to stimulation of the amygdala central nucleus in the anaesthetized rabbit.

1. The cardiovascular responses to electrical stimulation of the central nucleus of the amygdala (c.n.) have been studied in chloralose-anaesthetized rabbits. A pattern of response involving bradycardia, hypotension and hind-limb vasodilatation, accompanied by an increase in the rate of phrenic nerve discharge, was evoked only in response to stimulation within the medial portion of the c.n. 2. The cardiovascular responses were not secondary to the changes in respiratory activity since they were unaffected by altering central respiratory drive by either hypo- or hyperventilation of the animal. 3. The bradycardia was attenuated by the administration of atropine sulphate and abolished by the subsequent administration of propranolol, which when given alone attenuated the bradycardia. Atropine or propranolol given alone also attenuated the hypotension evoked by medial c.n. stimulation but the concurrent hind-limb vasodilatation was unaffected. 4. Atenolol, which unlike propranolol does not cross the blood-brain barrier, had little effect on the bradycardia in response to medial c.n. stimulation, but the subsequent administration of atropine abolished it. The hypotension in response to medial c.n. stimulation was also unaffected by atenolol. 5. The vasodilatation in response to medial c.n. stimulation was abolished by administration of guanethidine even after restoration of hind-limb perfusion pressure to control values by the infusion of angiotensin II into the hind-limb perfusion circuit. 6. Electrical stimulation of areas within 0.5 mm of the medial c.n. also resulted in bradycardia but then it was accompanied by hypertension and hind-limb vasoconstriction. Stimulation of areas 1.0 mm distant to the medial c.n. resulted in small and inconsistent cardiovascular responses. 7. These results show that hind-limb vasodilatation, mediated by withdrawal of sympathetic tone, occurs in response to stimulation within the medial c.n. of the rabbit and is in part responsible for the observed hypotension. It has also been confirmed that the bradycardia in response to medial c.n. stimulation is mediated by the vagus nerves.

Action Potentials↗
PubMed1987

Cardiovascular responses evoked from the fastigial region of the cerebellum in anaesthetized and decerebrate rabbits.

1. The rostral and caudal regions of the fastigial nucleus (f.n.) in both anaesthetized and decerebrate rabbits have been stimulated electrically while monitoring phrenic nerve activity, heart rate, blood pressure and blood flow to the kidney and hindlimb in addition to recording renal sympathetic nerve activity. 2. Stimulation of the rostral region of the f.n. in the anaesthetized and decerebrate rabbit produced a silencing of phrenic nerve discharge, either no change in heart rate or a vagally mediated bradycardia and a pressor response associated with vasoconstriction in both renal and femoral beds which resulted from an increase in sympathetic vasomotor tone. 3. Stimulation of the caudal region of the f.n. in the anaesthetized rabbit evoked apnoea and a bradycardia which was partially attenuated by vagal blockade. Also, a depressor response was obtained with no change in renal vascular resistance, a transient inhibition of renal sympathetic nerve discharge and a vasodilation in the hindlimb resulting from the withdrawal of sympathetic vasoconstrictor tone. In contrast, electrical stimulation of the same site in the unanaesthetized decerebrate rabbit evoked an increase in central inspiratory drive, a tachycardia and a pressor response with vasoconstriction in both vascular beds. The cardiac and vascular responses were abolished after sympathetic blockade. 4. Administration of a small dose of anaesthetic to the decerebrate preparation did not affect the direction of the cardiovascular or central respiratory responses evoked from the rostral f.n. but reversed the pattern of response elicited from the caudal f.n. to that seen in the intact anaesthetized rabbit. 5. The results of the present study suggest the existence of two separate regions associated with the f.n. which can influence the cardiovascular system in the rabbit. Furthermore, it would seem that the cardiovascular responses evoked from the vicinity of the caudal and rostral poles of the f.n. are mediated by two distinct pathways which might suggest two separate functional roles for the cerebellum in cardiovascular control in the rabbit.

Anesthesia, General↗
PubMed1987

Cardiovascular and respiratory responses evoked from the posterior cerebellar cortex and fastigial nucleus in the cat.

1. In both anaesthetized and decerebrate cats the cerebellar cortex (lobules VI, VII, VIII, IX and X) and the fastigial nucleus (f.n.) have been stimulated electrically, and chemically, while recording changes in phrenic nerve discharge, heart rate, arterial blood pressure and renal and femoral blood flow. 2. Stimulation of lobules VI, VII, VIII and Xb failed to elicit any cardiovascular or respiratory changes. Activation of lobule IX (the uvula), and in some preparations sub-lobule Xa, evoked cardiovascular and respiratory responses consistently. In the anaesthetized cat, electrical stimulation of the uvula evoked apnoea, a small bradycardia and a depressor response associated with vasodilatation in the hindlimb vascular bed. In contrast, stimulation in an equivalent region in a decerebrate preparation elicited an apneustic discharge, a pronounced tachycardia and a rise in arterial pressure with vasoconstriction in both renal and femoral vascular beds. In both the anaesthetized and decerebrate animals the pattern of response elicited by chemical activation was identical to that seen with electrical stimulation. 3. Electrical, or chemical, stimulation after administration of anaesthetic to the decerebrate cat then evoked an identical pattern of response to that seen in the 'intact' anaesthetized animal. This evidence suggests that the reversal in the pattern of the response in an effect of the anaesthetic agent and not the decerebration itself. 4. The only area of the f.n. to produce cardiovascular effects was the rostral region. Electrical stimulation of the rostral f.n. in both anaesthetized and decerebrate preparations inhibited central inspiratory activity and evoked tachycardia, along with a pressor response associated with vasoconstriction in both renal and femoral vascular beds. In contrast, chemical excitation of those sites in the rostral f.n. shown previously to produce pronounced cardiovascular and respiratory changes failed to elicit any changes in the recorded variables. 5. The present evidence suggests that there are two areas in the cat cerebellum which can exert pronounced cardiovascular and respiratory effects. The patterns of response elicited by electrical stimulation of the posterior cortex and rostral f.n. are mediated by two separate cerebellar-brainstem pathways as judged by the two different effects of anaesthesia on the evoked responses. We suggest that the f.n. may not play a role in the control of the cardiovascular system since chemical excitation of cell bodies of the rostral f.n. failed to elicit the so-called 'fastigial pressor response'.

Anesthesia, General↗
PubMed1986

Autoradiographic localization of alpha-adrenoceptors, muscarinic acetylcholine receptors and opiate receptors in the heart.

Using in vitro autoradiography the distribution of [3H]rauwolscine, [3H]prazosin and [3H]quinuclidinyl benzilate binding sites has been demonstrated in cardiac tissue taken from the cat and rat. A similar distribution of both alpha 1- and alpha 2-adrenoceptor sites was seen but the distribution of muscarinic acetylcholine sites was markedly different. alpha-Adrenoceptors were present predominantly in ventricular muscle whereas muscarinic acetylcholine receptors exhibited a greater density in atrial tissue compared to ventricular muscle. Opiate receptors were absent from cardiac tissue.

Animals↗