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Biomedical subjects

J H Coote

Publications and source records attributed to J H Coote.

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

The influence of 5-hydroxytryptamine agonists and antagonists on identified sympathetic preganglionic neurones in the rat, in vivo.

1. 5-Hydroxytryptamine (5-HT) was applied by microiontophoresis in the vicinity of identified sympathetic preganglionic neurones in the upper thoracic spinal cord of the rat, in vivo. 2. Sympathetic preganglionic neurones responded in one of three ways to 5-HT: by (a) excitation (76%), (b) inhibition (4%) or (c) in a biphasic manner (5%). 3. The excitatory responses evoked by 5-HT were mimicked by 5-carboxamidotryptamine (5-CT) and alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT). The inhibitory and biphasic responses evoked by 5-HT were mimicked by 2-methyl-5-hydroxytryptamine (2-Me-5-HT). The observed responses evoked by 5-HT and selective agonists may be different on the same cell. In several instances a single neurone excited by one agonist was inhibited by another agonist. 4. The 5-HT2-receptor antagonists, ketanserin and LY 53857, failed to abolish selectively the excitatory responses evoked by 5-HT and alpha-Me-5-HT, when applied by microiontophoresis. The antagonists non-selectively reduced the excitatory responses evoked by 5-HT, 5-CT, alpha-Me-5-HT, D,L-homocysteic acid (DLH) and noradrenaline (NA). A reduction in synaptically evoked activity was also observed. 5. The 5-HT3-receptor antagonist, ICS 205-930, failed to abolish the inhibitory responses evoked by 5-HT. 6. It was concluded that the excitatory responses evoked by 5-HT are mediated by a receptor that is neither 5-HT2 or 5-HT3, but shows similarities to the 5-HT1-like receptor profile. The inhibitory actions of 5-HT are mimicked by 2-Me-5-HT, but the receptor is not 5-HT3, or 5-HT1-like or 5-HT2.

Anesthesia↗
PubMed1990

Bulbospinal serotonergic pathways in the control of blood pressure.

The anatomy, physiology, and pharmacology of bulbospinal 5-HT neurons innervating spinal sympathetic cell groups are reviewed. On the basis of the location of 5-HT cell bodies, size of axons, type of synapse, and diversity of chemical coding, it is argued that the group of bulbospinal neurons is anatomically heterogenous. The evidence for both sympathoexcitatory and sympathoinhibitory actions of these neurons is discussed, and, although unequivocal evidence is still lacking, the idea of a functional heterogeneity is attractive. This is supported by observations that 5-HT also has both sympathoexcitatory and sympathoinhibitory actions in the spinal cord. These actions are mediated via two receptors, 5-HT1-like and 5-HT2, respectively. The question of whether or not these receptors are tonically activated is discussed, and it is shown that most evidence indicates they are not.

Animals↗
PubMed1989

Excitatory and inhibitory effects of epinephrine on neonatal rat sympathetic preganglionic neurons in vitro.

Current and voltage recordings were made from antidromically identified sympathetic preganglionic neurons (SPNs) in transverse thoracolumbar spinal cord slices removed from neonatal rats. When applied by either pressure ejection or superfusion, epinephrine (Epi) caused a slow depolarization or an inward current in 62 SPNs (42%) and a slow hyperpolarization or an outward current in 21 SPNs (14%). The responses persisted in low calcium- or tetrodotoxin-containing media. The Epi-induced depolarization or inward current was associated with increased membrane resistance; it was reduced by membrane hyperpolarization and nullified at a membrane potential of about -100 mV; a clear reversal however was not observed at more negative potential levels. In a number of SPNs the Epi-induced depolarization was accompanied by small inhibitory postsynaptic potentials. The latter were eliminated by a low calcium solution and by the glycine antagonist strychnine, suggesting that they were caused by glycine or a glycine-like substance released from interneurons subsequent to activation by Epi. The Epi-induced hyperpolarization or outward current was associated with decreased membrane resistance, and nullified around -100 mV. The alpha-adrenergic antagonist, dihydroergotamine, and alpha 1-antagonist, prazosin, reversibly blocked the excitatory, whereas the alpha 2-antagonist, yohimbine, abolished the inhibitory response, respectively. It is concluded that Epi acting on alpha 1- and alpha 2-adrenergic receptors depolarizes and hyperpolarizes the rat SPNs by decreasing or increasing membrane conductances to potassium ions.

Adrenergic Fibers↗
PubMed1989

Circulating atrial natriuretic factor activates vagal afferent inputs to paraventriculo-spinal neurones in the rat.

In urethane-anaesthetised, paralysed and artificially ventilated rats (300-350 g b.wt.), i.v. bolus injection of 3-5 micrograms atrial natriuretic factor (ANF) inhibited the activity of 5/8 (62.5%) antidromically identified spinally projecting neurones in the parvocellular portion of the hypothalamic paraventricular nucleus for periods of 6-40 min, mean 24 min. In contrast a much lower dose of ANF (250 ng) evoked a strong excitatory response in 37.5% of cells tested and either a weak inhibition or no effect on the remainder. Both inhibitory and excitatory effects were absent in bilaterally vagotomised animals. The results are discussed in relation to the role of circulating ANF in activating vagal afferent inputs to the paraventricular nucleus during volume loading.

Animals↗
PubMed1988

Electrophysiological properties of paraventriculo-spinal neurones in the rat.

In rats anaesthetized with urethane, electrical stimulation of the thoracic cord at T9-10 evoked antidromic response in neurones in the parvocellular portion of the ipsilateral paraventricular nucleus. Estimated conduction velocities in the spinally-projecting axons ranged from 0.6-5.9 m/sec. The majority (97%) of spinally projecting neurones were quiescent. Increases or decreases in the level of baroreceptor stimulation produced by intravenous injection of phenylephrine (1-5 micrograms) or sodium nitroprusside (10-15 micrograms) inhibited and excited amino acid-induced activity in 5/8 and 4/11 neurones respectively. Stimulation of vagal afferent endings by rapid bolus injection of 5-HT, to evoke the Bezold-Jarisch reflex. inhibited amino acid-induced activity in 15/18 cells. Activation of gastric vagal afferents by distension of the stomach had no effect on paraventriculo-spinal cells. It is suggested that at rest the excitability of paraventriculo-spinal neurones is depressed by a tonic inhibitory input which arises from vagal afferent fibres in the heart.

Action Potentials↗
PubMed1988

Effects of volume loading on paraventriculo-spinal neurones in the rat.

Experiments were carried out to investigate the effects of volume loading on the activity of antidromically identified paraventriculo-spinal neurones in rats anaesthetised with urethane. Intravenous infusion of isotonic saline (1.5-4.2 ml) inhibited amino acid induced activity in 12/20 cells. Of the remainder, 4 cells were excited and 4 were unaffected by volume loading. In 4/4 neurones inhibited by volume expansion, subsequent activation of vagal afferent nerve endings by i.v. bolus injection of 5-hydroxytryptamine (25-100 micrograms) also inhibited cell firing. The onset (0.5-7 min) and duration (5-29 min) of the inhibition evoked by volume loading showed considerable variation in different animals. The inhibitory effects of volume loading were absent in bilaterally vagotomised rats (n = 4). In these preparations the activity of paraventriculo-spinal neurones was facilitated by volume loading. It is suggested that during volume loading inhibitory vagally mediated inputs and excitatory non-vagal influences converge on paraventriculo-spinal neurones.

Afferent Pathways↗
PubMed1988

A comparison of the effects of intrathecally administered 5-hydroxytryptamine and thyrotropin-releasing hormone on renal and muscle sympathetic nerve activity.

Thyrotropin-releasing hormone (TRH) has been shown to coexist with 5-hydroxytryptamine (5-HT) in spinally projecting raphe neurones, some of which terminate in the sympathetic nuclei of the spinal cord. In an attempt to mimic the actions of these neurones, the effects of intrathecal administration of 5-HT was compared to that of TRH on activity in two sympathetic postganglionic nerves, the renal nerve and sympathetic fibres to skeletal muscle of the hind limb. In chloralose-urethane anaesthetised rats intrathecal infusion of TRH at the T9 level in doses of 5-30 micrograms increased activity in renal nerve as did low doses (20-100 micrograms) of 5-HT. In contrast, intrathecal infusion of TRH in doses of 5-30 micrograms and 5-HT in doses of 20-800 micrograms at L4 level decreased activity in sympathetic fibres to muscle. The results show that TRH, unlike 5-HT, has an excitatory but not an inhibitory action on renal sympathetic activity whereas both substances have only an inhibitory action on muscle sympathetic activity.

Adrenergic Fibers↗
PubMed1988

Excitatory and inhibitory actions of intrathecally administered 5-hydroxytryptamine on sympathetic nerve activity in the rat.

In chloralose/urethane anaesthetised rats the effect of intrathecal (i.t.) administration of 5-hydroxytryptamine (5-HT) on activity in sympathetic nerves to the kidney was studied. Intrathecal 5-HT (20-100 micrograms, 10 microliter) increased activity in renal nerves (mean change for 50 micrograms dose 157% +/- 39). At higher doses of 5-HT the initial excitatory response was followed by inhibition 64% +/- 15. Intrathecally, alpha methyl 5-HT (10-400 micrograms) mimicked only the inhibitory action of 5-HT in a dose-dependent manner. These inhibitions were completely antagonised by i.t. ketanserin (25-100 micrograms). Intrathecal 2 methyl 5-HT (10-200 micrograms) had little effect on renal nerve activity. Intrathecal 5 carboxyamidotryptamine (10-200 micrograms) had a more powerful excitatory action on renal nerve activity than did 5-HT. Intrathecally, 8 OH-DPAT (10-200 micrograms) was without effect. Neither the inhibitory action of 5-HT or the excitatory action was affected by i.t. ICS 205 930 (1-10 micrograms) or MDL 72222 (200 micrograms). It was concluded that the actions of 5-HT were within the spinal cord and that the inhibitory effect on sympathetic activity is mediated via a 5-HT2-like receptor whilst the receptors involved in the excitatory action of 5-HT are not M- or 5-HT3-like but appear to be more like the 5-HT1 subtype.

Animals↗
PubMed1988

Patterns of activity in sympathetic postganglionic nerves to skeletal muscle, skin and kidney during stimulation of the medullary raphe area of the rat.

In chloralose/urethane anaesthetised rats multi and single fibre activity was recorded in renal sympathetic nerves and in sympathetic nerves to skeletal muscle and to the skin of the hind limb. The activity was pulse-modulated and inhibited by stimulating baroreceptors with an increase in blood pressure following i.v. phenylephrine. The study investigated the effect of stimulating medial regions of the lower brainstem on activity in these sympathetic nerves. Comparing renal nerve and skin sympathetic nerve activity two main patterns of response were seen, either an inhibition of both or excitation of both. In contrast when comparing renal nerve activity with muscle sympathetic nerve activity a third pattern was evoked from a few sites located in nucleus raphe obscurus, an inhibition of renal nerve activity and excitation of muscle sympathetic activity. The latter is the same pattern as that evoked in the cat. Unlike the cat, however, the decerebrate rat was not observed to generate this differential pattern of activity either spontaneously or following the administration of physostigmine. It is argued that the activation of cell bodies located in raphe obscurus is responsible for inducing a pattern of sympathetic activity similar to that occurring during paradoxical sleep in other animals.

Animals↗
PubMed1988

Effects of activating spinal alpha-adrenoreceptors on sympathetic nerve activity in the rat.

The effects of several alpha-adrenoreceptor agonists and antagonists administered intrathecally at T10 level on renal sympathetic nerve activity (RSNA) were examined, in chloralose-urethane anaesthetised rats. Intrathecal noradrenaline (NA, 0.5-500 micrograms) produced one of 3 responses depending on dose, an inhibition of RSNA at low doses, an excitation of RSNA at high doses, or a biphasic effect. Intrathecal adrenaline (5-200 micrograms) was inhibitory in the main but some doses elicited poorly repeatable brief excitation followed by prolonged inhibition. Intrathecal methoxamine (ME; 2.5 ng-25 micrograms) caused a dose-dependent increase in RSNA (mean maximum response 27 +/- 0.5%). The excitatory effects of NA and ME were blocked (72% +/- 12%) by pretreatment with intrathecal prazosin (PRA, 20-200 ng) but not by yohimbine (YOH, 200 ng). Intrathecal guanabenz (GUA 3-15 micrograms) caused a dose-dependent inhibitory effect on RSNA (mean maximum 32% +/- 5%). The inhibitory effects of NA, adrenaline and GUA were blocked by pretreatment with intrathecal YOH (200 ng-2 micrograms). Intrathecal PRA (200 ng) had no effect on the inhibitory effects of NA and GUA. Intravenous administration of each of the adrenoreceptor agonists (apart from adrenaline), at similar doses to those given intrathecally, in most cases had no significant effect on RSNA; in a few cases the opposite effects to those produced by intrathecal administration were seen.

Adrenergic alpha-Agonists↗
PubMed1988

Altitude insomnia: studies during an expedition to the Himalayas.

During an expedition to the Himalayas, we studied the sleep and respiration of six climbers. Three ingested acetazolamide (500 mg) daily throughout the climb and the other three ingested placebo. At high altitude (4,150-4,846 m), each subject ingested temazepam (10 mg) for one night and placebo for another. Acetazolamide improved sleep above 2,750 m, but it is uncertain whether this was due to sedation or to improvements in arterial oxygen saturation. Sleep was markedly disturbed in all subjects above 4,000 m. Temazepam improved sleep, and in subjects taking acetazolamide, it reduced sleep-onset latencies and increased sleep efficiency close to that of sea level values. These observations suggest that the prophylactic use of acetazolamide is likely to improve sleep in climbers and that a low dose of a benzodiazepine such as temazepam (10 mg) may be beneficial at high altitude. Studies are now needed to exclude any possibility of respiratory impairment at altitude before a firm recommendation can be made regarding the routine use of this hypnotic.

Acetazolamide↗
PubMed1987

The action of a substance P antagonist on sympathetic nerve activity in the rat.

In anaesthetised rats recordings were made of sympathetic activity in renal nerves whilst studying the effects of intrathecal injection of the substance P antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-substance P on the responses to, stimulation of the ventrolateral medulla, to intrathecal injection of substance P, serotonin and glutamate. All responses were abolished by the antagonist.

Animals↗
PubMed1987

Intrathecally administered angiotensin II increases sympathetic activity in the rat.

The possibility that angiotensin II (AII) functions as an excitatory transmitter on sympathetic preganglionic neurones was tested in anaesthetized rats. Drugs were administered intrathecally whilst recording blood pressure, heart rate and sympathetic activity in splanchnic or renal nerves. Intrathecal AII (20 microliters, 10(-5) M) caused a significant increase in blood pressure of 13% +/- 3 and in sympathetic activity of 15% +/- 5. Intrathecal AII (20 microliters, 10(-3) M) caused larger increases in blood pressure of 22% +/- 3 and in sympathetic activity of 25% +/- 3. The magnitude of the response was dependent on the location of the catheter tip within the subarachnoid space T9-T11 being best for the above changes. Preceding intrathecal AII with the AII antagonist Saralasin (20 microliters, 10(-3) M) also given intrathecally prevented the changes. An increase in sympathetic nerve activity brought about reflexly by a drop in blood pressure of 45-47 mm Hg was almost halved by intrathecal Saralasin. Peak plasma counts (less than 5% of total) of [3H]AII in the blood after intrathecal injection occurred 2 min after the peak changes in sympathetic activity and blood pressure. Counts of [3H]AII in the spinal cord showed that 81% of recovered label was within one segment on either side of the catheter tip. It is concluded that AII has an excitatory action on sympathetic neurones in the spinal cord.

Angiotensin II↗
PubMed1987

The BMRES 1984 Medical Research Expedition to the Himalayas.

Twenty-one subjects formed a trekking expedition to study the effects of acetazolamide on exercise performance and acclimatization at high altitude. Subjects were randomized to acetazolamide or placebo on a double blind basis. During ascent to and stay for 6 nights at 4846 m studies were carried out on blood gases, 2,3 diphosphoglycerate (2,3 DPG), proteinuria, exercise testing, intestinal absorption, purine metabolism and changes in body composition. The results showed beneficial effects of acetazolamide on exercise performance and preservation of muscle mass.

Acclimatization↗
PubMed1987

Blood lactate changes during exercise at high altitude.

Blood lactate concentrations were measured in 18 normal subjects at the end of an exercise test designed to maintain heart rate at 85% of maximum for 15 minutes. Blood lactate concentrations were reduced at high altitude (4846 m) and correlated positively with basal pH and negatively with basal Pa,O2 levels. Blood lactate concentrations tended to be lower in those subjects on acetazolamide but were not correlated with the severity of acute mountain sickness or with the workload of the exercise test. We conclude that the pH changes are probably the most significant factor in reducing lactate concentrations.

Acetazolamide↗
PubMed1987

The effect of acetazolamide on breath holding at high altitude.

The effect of altitude and acetazolamide on breath holding was studied in 20 individuals. Breath holding time was reduced progressively during ascent. There was an additional reduction in the acetazolamide group at low but not at high altitude. The initial difference between the two groups may have been related to a lower CSF pH when on acetazolamide. At high altitude the finding of similar breath holding times in the two groups may have been due to acclimatization in the placebo group.

Acetazolamide↗
PubMed1986

Discharge patterns in postganglionic neurones to skeletal muscle and kidney during activation of the hypothalamic and midbrain defence areas in the cat.

Electrical stimulation of hypothalamic and midbrain defence area sites eliciting a cholinergic vasodilatation in the hindlimb activates vasodilator fibres supplying skeletal muscle. Simultaneous baroreceptor mediated suppression of sympathetic vasoconstrictor activity to the muscle and postfiring depression of vasoconstrictor activity contribute to the development of the vasodilatation during and after the stimulus. The observation of a differential pattern of activation of muscle and renal vasoconstrictor fibres implies a reciprocal influence exerted on these sympathetic outflows by neurones in the defence areas of the brain.

Aggression↗