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Biomedical subjects

J H Coote

Publications and source records attributed to J H Coote.

At least 127 records · Page 7Linked to original sources

The contribution of brain stem catecholamine cell groups to the innervation of the sympathetic lateral cell column.

Data are presented on the quantitative distribution of individual catecholamines, noradrenaline (NA), dopamine (DA) and adrenaline (A) determined within specific microdissected areas of the third thoracic segment of the cat spinal cord, using a radioenzymatic assay. NA was found in much higher concentrations than the other catecholamines with highest levels in medial-ventral grey matter (754 +/- 56 ng/100 mg protein) and in dorsal and intermediolateral grey matter. DA was present in much smaller amounts, but was relatively concentrated in medial and dorsal grey matter (up to 76 +/- 1 ng/100 mg protein). Very little A was detected ( less than 17 ng/100 mg protein). Experiments were carried out to determine the contribution made by various brain stem cell groups to the catecholamine innervation of the spinal cord, and in particular the sympathetic lateral column. The concentrations of the catecholamines was determined in 5 groups of animals, 3-5 days after decerebration, or decerebration together with bilateral lesions of the A1, A2, A5 or A6 groups. A major and selective NA input to the sympathetic lateral column from the A1 cell group was revealed. There may also be a small contribution from the A2 and A6 groups, but none was shown from the A5 group. The A6 group was also shown to provide a selective noradrenergic input to the ventral horn. Some evidence is presented for the origin of noradrenergic inputs to other regions, e.g. dorsal horn. The possibility of a separate dopaminergic innervation to specific regions of the spinal cord is discussed.

Adrenergic Fibers↗

Comparison of the antihypertensive effects of indapamide and metoprolol.

The effects on blood pressure and heart rate of 200 mg metoprolol and 2.5 mg indapamide given separately and together as a single daily dose were compared in 27 patients suffering from moderate hypertension. The blood pressure and heart rate were measured in the lying and standing position, before, during and after exercise. Both indapamide and metoprolol in a single daily dose reduced the blood pressure. The best results were achieved by a combination of the two.

Adult↗

Intracellular recordings from sympathetic preganglionic neurones.

In anaesthetised cats the response of the soma dendritic region of sympathetic preganglionic neurones (SPN) recorded intracellularly in T3 spinal segment was studied following excitation of third thoracic white ramus and following orthodromic inputs. Most cells had action potentials of short duration. Many cells were active. Decreases in membrane potential were relatively short lasting, less than 40 msec and a change of 5 mV was sufficient to discharge the cell. Increases in membrane potential were also evident.

Animals↗

Inhibition of the baroreceptor reflex on stimulation in the brain stem defence centre.

1. In anaesthetized cats, the pattern of cardiovascular response characteristic of the defence reaction has been elicited by localized electrical stimulation within the appropriate region of the hypothalamus. The baroreceptor reflex response has been elicited by raising the pressure in a blind sac preparation of the carotid sinus or by electrical stimulation of the sinus nerve.2. In addition to arterial blood pressure, heart rate and regional blood flows, activity was recorded in cardiac and renal sympathetic nerves, to assess more precisely the cardiomotor and vasomotor changes during interactions between brain stem stimulation and baroreceptor activation.3. The sympatho-inhibitory and depressor effects of carotid sinus stimulation or electrical stimulation of the sinus nerve could be completely suppressed by stimulation within the hypothalamic defence area, as could the reflex bradycardia. It is concluded that this suppression is effected through the central nervous system.4. Stimulation at points in the hypothalamus close to, but outside, the defence area, and which elicited increases in arterial pressure and sympathetic activity of similar magnitude to those from the defence area itself, did not abolish the sympatho-inhibitory or depressor effects of baroreceptor activation, though the reflex bradycardia was usually inhibited. It is suggested that this less localized change results from augmentation of the central inspiratory drive which inhibits the vagal outflow to the heart.

Action Potentials↗

Bulbospinal tryptaminergic neurones. A search for the role of bulbospinal tryptaminergic neurones in the control of sympathetic activity.

1. The possible role of bulbospinal tryptaminergic neurones in the control of sympathetic activity has been investigated in anaesthetised cats. 2. Depletion of spinal cord stores of 5-hydroxytryptamine was achieved by systemic administration of p-chlorophenylalanine or by intraspinal microinjections of 5,6-dihydroxytryptamine. 3. Blood pressure was little changed by these treatments, neither was the pattern of ongoing activity in sympathetic nerves (arterial pulse rhythmicity and respiratory modulation), the influence of pulmonary afferent nerves on this activity (determined by an airway occlusion technique), the sympatho-inhibitory influence of the carotid sinus baroreceptors, nor the sympatho-inhibitory or -excitatory influences of somatic afferent nerves. 4. Since both p-chlorophenylalanine and 5,6-dihydroxytryptamine treatment caused extensive disruption of the bulbospinal tryptaminergic neurones, it was concluded that these play no significant role in the mediation of the responses tested in anaesthetised cats in the present study.

5,6-Dihydroxytryptamine↗

Supraspinal regulation of spinal reflex discharge into cardiac sympathetic nerves.

(1) In chloralose anaesthetized cats, reflex responses were recorded in inferior cardiac nerves following stimulation of intercostal nerves and hind limb afferent nerves. (2) In 80% of cats, a long latency reflex response alone was recorded, whereas, in the others, a short and long latency response was present to intercostal nerve stimulation. (3) In cats displaying only a long latency somatocardiac reflex response, damage to the ventral quadrant of the ipsilateral cervical spinal cord, through which runs a bulbospinal inhibitory pathway, resulted in the appearance of shorter latency reflexes to intercostal nerve stimulation. Lesions elsewhere in the cervical cord did not do this. (4) The characteristics of the early responses indicated that they were somatosympathetic reflexes and not dorsal root reflexes. (5) The early reflexes remained and the late reflex disappeared on subsequent complete transection of the spinal cord. The early reflexes were therefore spinal reflexes, and suppressed in the animal with cord intact. (6) Lesions at C4, which included a contralateral hemisection and a section of dorsal columns extending into the dorsal part of the lateral funiculus, abolished the inhibition of a sympathetic reflex that followed stimulation of some somatic afferent nerve fibres. These sections did not release the spinal reflex. Therefore, this reflex inhibition was not responsible for the suppression of the spinal somatosympathetic reflex. (7) The descending inhibitory influence on the segmental reflex pathway was not antagonized by strychnine, bicuculline or picrotoxin. (8) The possibility is discussed that the spinal reflex pathway into cardiac sympathetic nerves is tonically inhibited by a bulbospinal pathway originating from the classical depressor region of the ventromedial reticular formation.

Animals↗

The effect of intraspinal microinjections of 6-hydroxydopamine on the inhibitory influence exerted on spinal sympathetic activity by the baroreceptors.

1. The inhibition of spinal somato-sympathetic reflex activity, following electrical stimulation of the carotid sinus nerve in cats has been studied before and after chronic intraspinal microinjections of 6-hydroxydopamine into the cervical spinal cord. 2. The effect of these microinjections on bulbospinal catecholaminergic neurones was assessed using the formaldehyde fluorescence technique for the demonstration of intraneuronal monoamines. 3. In 5 6-hydroxydopamine-treated animals, inhibition of the spinal sympathetic reflex response following stimulation of the sinus nerve was reduced compared to control untreated animals. When damage to the bulbo-spinal catecholamine system in the dorso-lateral funiculi was extensive, the inhibition was almost completely abolished; with more limited destruction a lesser effect was observed. 4. These effects were not seen in a group of control animals, which received intraspinal microinjections of the 5-hydroxytryptamine neurotoxin 5,6-dihydroxytryptamine and which showed damage to the indoleaminergic neuronal system but no damage to the bulbo-spinal catecholaminergic system. 5. It is concluded that the inhibitory effects of the baroreceptors on spinal sympathetic activity are mediated by bulbo-spinal catecholaminergic neurones.

Animals↗

Reflex regulation of sympathetic activity in the spontaneously hypertensive rat.

The influence that the pressure-sensitive receptors in the cardiovascular system have on renal nerve activity and on heart rate was compared in normotensive rats (NTR) and spontaneously hypertensive rats (SHR). The cardiovascular receptors were stimulated by raising the blood pressure (BP) with intravenous phenylephrine. The duration of silence in the record of renal sympathetic nerve activity produced by a number of different rises in BP was measured. We found that the pressure that was just able to produce a silence in the nerve activity (threshold pressure) was higher in the SHR (170 mm Hg) than in the NTR (130 mm Hg). Also, comparable rises in BP above the threshold pressure in the SHR and NTR were less effective in the SHR in producing a complete inhibition of sympathetic nerve activity as judged by the short duration of inhibition. In contrast, we found that the changes in heart rate produced by rises in BP above threshold pressure were similar in NTR and SHR although the threshold pressure was somewhat higher in the latter. It was, therefore, concluded that the cardiovascular pressure receptors, apart from being reset to operate at a higher pressure level in the SHR, are less able to inhibit ongoing sympathetic activity than in the NTR. It is suggested that this is most likely due to a high sympathetic activity in the SHR.

Animals↗

The baroreceptor reflex and the cardiovascular changes associated with sustained muscular contraction in the cat.

In decerebrate unanaesthetised cats the cardiovascular effects of raising the pressure in a blind sac preparation of a carotid sinus on one side were examined at rest and during sustained contractions of hind-limb muscles. During a tetanic contraction the absolute value of the blood pressure and heart-rate components of the baroreceptor reflex response were not significantly changed from those at rest. The curve relating heart-rate and mean blood pressure, during carotid sinus distension, was similar at rest and when the muscles of the hind-limb were contracting tetanically, although each value of heart-rate was greater, suggesting a resetting of the baroreceptor reflex. By contrast, in the same experiments, suppression of the baroreceptor reflex changes in heart-rate and blood pressure could be demonstrated during the increases of blood pressure and heart-rate elicited by the afferent discharge from muscles during sustained contraction are buffered to some extent by the baroreceptors, though their inhibitoru effect is incomplete under these conditions.

Animals↗

The spinal route of sympatho-inhibitory pathways descending from the medulla oblongata.

1. The effect of making discrete lesions in the cervical spinal cord on the brainstem elicited inhibition of a spinal somato-sympathetic reflex response has been studied in anaesthetized cats. 2. Electrical stimulation within three areas of the medulla caused an inhibition of the spinal component of the reflex response elicited in thoracic white rami communicantes by stimulation of intercostal nerves. The three medullary areas studied were the ventrolateral medulla and the caudal rephe nucleus, from where bulbospinal monoamine neurones originate, and the ventromedial reticular formation. 3. The inhibitory effects of stimulation in the ventrolateral medulla and raphe nucleus were abolished by the destruction of parts of the ipsilateral dorsolateral funiculus of the cervical spinal cord, whereas the inhibition produced by ventromedial reticular formation stimulation was abolished by lesions which included part of the ventral quadrant of the cord. 4. The time course of the inhibitory effects of electrical stimulation of descending sympatho-inhibitory tracts in the cervical spinal cord was studied in unanaesthetized decerebrate cats spinalized at C1. Inhibition obtained from the dorsolateral funiculus characteristically had a longer time to onset than inhibition obtained from the ventrolateral and ventral funiculi.

Animals↗

The influence of bulbospinal monoaminergic pathways on sympathetic nerve activity.

1. Spontaneous and reflex activity was recorded from renal and splanchnic nerves and thoracic white rami during discrete electrical stimulation within the medulla oblongata of anaesthetized cats.2. Inhibition or excitation of spontaneous sympathetic nerve activity was obtained from several medullary regions.3. The long-circuited reflex elicited in renal nerves and the spinally mediated reflex discharge produced in white rami by single shock stimulation of intercostal nerves were inhibited by stimulation within the sympatho-inhibitory areas of the medulla.4. Activation of spontaneous sympathetic nerve activity or inhibition of spontaneous and reflex sympathetic nerve activity was obtained during electrical stimulation within the lateral funiculi of the cervical spinal cord in unanaesthetized decerebrate cats, spinalized at C1.5. There was a correlation between the position of some sympatho-inhibitory regions of the medulla and spinal cord and the position of the cell bodies and axons of descending monoamine-containing neurones.6. Intravenous administration of the precursor of noradrenaline, L-DOPA, to unanaesthetized decerebrate cats, spinalized at C1, was followed by a depression of spontaneous activity in renal nerves and reflex responses elicited in renal nerves and white rami.7. Similarly the precursor of 5-hydroxytryptamine, 5-HTP, caused a depression of reflex activity elicited in renal nerves and white rami, but had no effect on spontaneous renal nerve activity.8. It is suggested that there exist both noradrenergic and tryptaminergic pathways which descend to the spinal cord from the medulla and which are inhibitory to sympathetic outflow.

5-Hydroxytryptophan↗

Evidence for the involvement in the baroreceptor reflex of a descending inhibitory pathway.

1. The onset and time course of baroreceptor inhibition of pre- and post-ganglionic sympathetic reflex activity has been examined in the anaesthetized cat.2. The shortest time to the onset of inhibition of an intercostal evoked reflex response in cardiac and renal nerve was less than 90 msec following a rise in pressure in a carotid sinus blind sac, and around 55 msec following stimulation of the ipsilateral sinus nerve. The cardiac nerve response was completely inhibited before the renal nerve response.3. Because of the long delays in the somato-sympathetic reflex pathway it is argued that these minimum times will be much less than the real central delay of baroreceptor inhibition. These were estimated by adding on the central times for the somato-sympathetic reflexes to give latencies of 94-143 msec for the inhibition.4. A spinal sympathetic reflex was inhibited by 30-75% following a rise in pressure in a carotid sinus blind sac or sinus nerve stimulation. The minimum time for this inhibition was around 100 msec.5. The baroreceptor inhibition of the spinal sympathetic reflex was abolished following section of a restricted region in the dorsolateral part of the lateral funiculus of the cervical spinal cord.6. Both pre- and post-ganglionic reflexes could be inhibited when stimulating within three regions of the medulla oblongata. The latency to inhibition elicited from the ventromedial reticular formation was short, some 5-30 msec, whereas that elicited from a ventrolateral region or the mid line raphe nucleus was long, some 90-160 msec.7. The possibility is discussed that the baroreceptor inhibition of both the pre- and post-ganglionic reflexes examined in this study is occurring at the spinal level via a pathway from either the raphe nuclei or ventrolateral medulla.

Animals↗