Biomedical subjects

L F Arnolda

Publications and source records attributed to L F Arnolda.

30 records · Page 2Linked to original sources

PubMed1996

Tachycardia after glutamate injection in rat spinal cord is not blocked by kynurenate or mimicked by metabotropic agonists.

1. We have used microinjections of glutamate, an ionotropic excitatory amino acid receptor antagonist (kynurenate) and selective ionotropic (NMDA and kainate) and metabotropic (1S-3R-ACPD, trans-ACPD and L-AP4) receptor agonists in the thoracic IML of the rat to define the receptors mediating the tachycardia produced by excitatory amino acid antagonists. 2. Injection of glutamate (delta heart rate = 76 +/- 8 beats/min n = 16), NMDA (delta heart rate = 116.5 +/- 5 beats/min n = 6) or kainate (delta heart rate = 92 +/- 22 beats/min n =6 evokes a tachycardia when injected into the thoracic intermediolateral column. Kynurenate blocked the response to NMDA (-2% of initial response) and markedly attenuated the response to kainate (14% of initial response) but did not alter the response to glutamate (106% of initial response). 3. IS-3R-ACPD did not elicit a tachycardia when injected into the thoracic intermediolateral column and neither trans-ACPD nor L-AP4 induced a tachycardia after kynurenate injection into the thoracic intermediolateral column. 4. Thus stimulation of either NMDA or AMPA/kainate receptors elicits tachycardia in rat thoracic spinal cord but glutamate also activates another receptor type to elicit a tachycardia. The lack of a tachycardia when trans-ACPD, 1S-3R-ACPD or L-AP4 were injected into the thoracic spinal cord suggests that the kynurenate resistant tachycardia elicited by glutamate is not mediated by metabotropic receptors. The kynurenate resistant tachycardia elicited by glutamate is not mediated by any of the known excitatory amino acid receptor types.

Aminobutyrates↗

PubMed1995

Bulbospinal sympatho-excitatory neurons in the rat caudal raphe.

OBJECTIVES: To explore the rat caudal raphe nuclei for neurons that respond to activation of baroreceptor nerves and that have a spinal axon, and to compare the behavioural properties of barosensitive bulbospinal neurons in the rat caudal raphe with the properties of barosensitive bulbospinal neurons in the rostral ventrolateral medulla. DESIGN: Extracellular unit recordings were obtained from an area extending up to 1.0 mm caudally from the caudal edge of the facial nucleus. Two sites were explored: the rostral ventrolateral medulla and the midline. MATERIALS AND METHODS: Single-unit recordings were made in anaesthetized (75 mg/kg chloral hydrate and 30 mg/kg sodium pentobarbitone then 3-6 mg intravenously as required), immobilized (2 mg pancuronium as required) Sprague-Dawley rats. Central respiratory drive was recorded from phrenic nerve discharge. The barosensitivity of single units was assessed by R-wave triggered histograms and by histograms of their responses to aortic nerve stimulation or to intravenous injection of phenylephrine. Nociceptors were activated by a brief pinch of the tail. RESULTS: Eleven spontaneously active units in the midline that were inhibited by baroreceptor stimulation and had a spinal axon were studied. Respiratory modulation was present and was predominantly inspiratory. Barosensitive neurons in the rostral ventrolateral medulla were activated by nociceptive inputs; midline barosensitive neurons were not. CONCLUSIONS: The behavioural characteristics of midline neurons differ from those of the bulbospinal barosensitive neurons in the rostral ventrolateral medulla, indicating that raphe spinal neurons have different sets of afferent inputs and may subserve to a distinct physiological role. The present paper is the first report of bulbospinal neurons in the rat caudal raphe that are inhibited by activation of arterial baroreceptors.

Adrenergic Fibers↗

PubMed1994

Disinhibition of the rostral ventral medulla increases blood pressure and Fos expression in bulbospinal neurons.

The GABA agonist muscimol, injected into the depressor area of the caudal ventrolateral medulla, increased blood pressure and increased the expression of the immediate early gene c-fos in the rostral ventral medulla (RVM) of the rat. The number of Fos-immunoreactive (Fos-IR) neurons seen in the RVM was increased 3-fold after muscimol compared to Fos-IR after vehicle treatment. In the rostral aspect of the RVM approximately half of the Fos-IR neurons were identified as spinally projecting after the injection of the retrograde tracer cholera toxin B subunit into the upper thoracic spinal cord. These bulbospinal Fos-IR neurons were identified in the lateral aspects of the RVM, in the area where baroreceptor-sensitive neurons have been identified in electrophysiological studies, and also in more medial areas of the RVM. Fos-IR neurons were also identified in the intermediolateral cell column of the thoracic spinal cord after muscimol injection, but were rarely observed in this area after vehicle treatment. This study demonstrates the functional connectivity of the caudal and rostral areas of the medulla oblongata and the spinal cord, supporting the view that the caudal ventrolateral medulla contains neurons that provide a tonic inhibitory control over neurons in the RVM and that, in turn, the spinally projecting neurons in the RVM provide an excitatory input to the spinal cord sympathetic preganglionic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Lack of effect of atrial natriuretic peptide on vasopressin release.

This study was designed to investigate the effects of intracerebroventricular or intravenous atrial natriuretic peptide (ANP) on plasma arginine-vasopressin (AVP) levels, plasma renin activity (PRA), blood pressure (BP) and heart rate (HR) in conscious rats. No changes were observed in plasma AVP levels and PRA after intracerebroventricular injection of ANP (0.3 nmol/kg). Also no changes were found in BP and HR after intracerebroventricular ANP injection in the dose range 0.01-0.3 nmol/kg. No significant changes were observed in plasma AVP levels after the intravenous administration of ANP at 2.5 nmol/kg to hydrated rats or at 0.1 nmol/kg and 2.5 nmol/kg to dehydrated rats, although the larger dose was sufficient to cause a small fall in BP. Even after 30 min intravenous infusion of ANP at 0.1 nmol min-1 kg-1, a dose sufficient to produce very high plasma ANP levels, no change in plasma AVP could be detected, although haemodynamic changes were observed. Intravenous ANP injection (2.5 nmol/kg) inhibited basal renin secretion in hydrated rats and also inhibited renin secretion which had been stimulated by prior dehydration. From these studies in hydrated and dehydrated rats, there was no evidence that either intracerebroventricular or intravenous ANP administration affected AVP release in vivo.

Animals↗

PubMed1987

Responses of vasoactive hormones in congestive cardiac failure.

Congestive cardiac failure causes activation of various neurohumoral responses that increase total peripheral resistance and promote salt and water retention. These effects increase blood pressure and organ perfusion in the short term, but ultimately cause further cardiac decompensation by increasing ventricular afterload and cardiac work. The role of the renin-angiotensin-aldosterone system and the catecholamines is partially understood, and blockade of these systems as a treatment of heart failure is now established. The role of vasopressin in heart failure is more controversial, but there is now compelling evidence that vasopressin may have important vasoconstrictor actions in addition to its fluid retaining properties. Atrial natriuretic factor is a newly described cardiac hormone released from the atrium. Atrial natriuretic factor causes natriuresis, diuresis, vasodilatation, suppression of thirst, and suppression of both renin and aldosterone. These actions largely counteract the effects of the renin-angiotensin system and vasopressin. Plasma atrial natriuretic factor has been reported to be markedly elevated in human and experimental heart failure, and may act to limit the neurohumoral response to reduced cardiac output. This review summarizes our understanding of the vasoactive hormones and reports experimental evidence supporting a pathophysiological role for vasopressin and atrial natriuretic factor in congestive cardiac failure.

Animals↗

PubMed1986

Enalapril reduces the catecholamine response to exercise in patients with heart failure.

Increased sympathetic activity occurs in congestive heart failure and may have deleterious effects. To examine the effects of angiotensin converting enzyme (ACE) inhibition on sympathetic activity in heart failure, the noradrenaline response to exercise was measured in 18 patients given enalapril or placebo in double-blind trial. The plasma noradrenaline response to graded exercise was significantly reduced after 4 weeks on active treatment but was unchanged by placebo treatment. The rate-pressure product at maximal exercise was significantly reduced after 4 weeks in the enalapril group but unchanged in the placebo group. These results suggest that ACE inhibition reduces sympathetic activity in patients with heart failure.

Aged↗

PubMed1983

Acute amphetamine cardiomyopathy in a drug addict.

A case of acute left ventricular failure following an intravenous dose of amphetamine is described. The diagnosis was made by right heart catheterization. This is the first description of acute amphetamine cardiomyopathy in the medical literature.

Acute Disease↗

PubMedDate not supplied

c-fos expression in central cardiovascular pathways.

Injection of muscimol in the caudal ventrolateral medulla increases blood pressure and stimulates neuronal c-fos expression in the rostral ventral medulla (RVM). The blockade of c-fos expression in the RVM by antisense oligonucleotides attenuates the blood pressure response to this muscimol-induced disinhibition of the RVM and also reduces resting blood pressure. The results suggest that cardiovascular neurons in the RVM express c-fos and that the basal and stimulated expression of the c-fos gene is important in the central regulation of blood pressure.

Animals↗

PubMedDate not supplied

The one hundred percent hypothesis: glutamate or GABA in synapses on sympathetic preganglionic neurons.

The synaptic input from glutamate- or gamma-aminobutyric acid (GABA)-immunoreactive nerve fibers to sympathetic preganglionic neurons projecting to the superior cervical ganglion was assessed using retrograde tracing with cholera toxin B subunit and post-embedding immunogold labelling. Half the boutons that synapsed on or directly contacted this group of neurons were immunoreactive for glutamate and half were immunoreactive for GABA. In previous studies, about 2/3 of the synapses on sympathoadrenal neurons were found to be glutamate-immunoreactive and about 1/3, GABA immunoreactive and these two amino acids were not co-localized. Thus, 100% of the boutons that synapse on sympathetic preganglionic neurons supplying the superior cervical ganglion or the adrenal medulla are likely to contain either glutamate or GABA. Anterograde tracing combined with amino acid immunocytochemistry indicated that at least some glutamate-containing and some GABA-containing nerve fibers in the intermediolateral cell column could come from the rostral ventral medulla.

Animals↗

PubMedDate not supplied

Substance P and serotonergic inputs to sympathetic preganglionic neurons.

Sympathetic preganglionic neurons are the final central links in the sympathetic pathways that control the heart and blood vessels. The neurotransmitters present in the supraspinal pathways that control the activity of sympathetic preganglionic neurons include amino acids, amines and peptides. In this paper we discuss evidence that suggests a role for serotonin and substance P in these pathways. Both of these neurotransmitters are present in bulbospinal neurons. Our results suggest that they have an important physiological role in the central regulation of blood pressure.

Animals↗

PubMedDate not supplied

Immediate early genes in blood pressure regulation.

The immediate early genes c-fos and c-jun are transcription regulating factors. c-fos expression is widely used as a marker of neuronal activation and has been used in this study to identify those neurons, presumably vasomotor neurons, that are activated after interventions that alter blood pressure. c-fos and c-jun are expressed in the rostral ventral medulla (RVM) when the tonically active inhibitory inputs to the RVM are removed, either acutely or chronically, as in the SHR model of gentic hypertension. The injection of antisense oligonucleotide complementary to c-fos mRNA in the RVM attenuates the expression of c-fos, lowers resting blood pressure and attenuates blood pressure responses that are evoked via RVM mechanisms. These studies suggest a link between immediate early gene expression in neurons in the RVM and the regulation of blood pressure. c-fos could have an important role in regulating the activity of these central cardiovascular neurons. The role of the immediate early gene c-jun in cardiovascular control remains to be elucidated.

Animals↗

PubMedDate not supplied

C-fos expression in central neurons mediating the arterial baroreceptor reflex.

The immediate early gene c-fos is a transcription regulating factor that is widely employed as a marker of neuronal activation. In this study we have used c-fos expression to identify vasomotor neurons in the brainstem and spinal cord that are activated after interventions that alter blood pressure. These neurons are likely to be those that subserve the arterial baroreceptor reflex and maintain blood pressure within a defined range. With the combination of Fos expression and neuronal tracing, we describe the location and central connections of these neurons. The differential expression of Fos in neurons in separate regions of the brainstem and spinal cord, after either hypotensive or hypertensive stimuli in conscious rats, supports current opinion about baroreflex circuitry. The central processes of baroafferent neurons synapse with second order baroreflex neurons in the nucleus tractus solitarius. From this region baroreceptor information is transmitted to neurons in the caudal ventrolateral medulla and then to neurons in the rostral ventrolateral medulla. The sympathetic preganglionic neurons in the intermediolateral column of the thoracolumbar spinal cord are the final crucial site involved in the arterial baroreflex.

Adrenergic alpha-Agonists↗