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P M Pilowsky

Publications and source records attributed to P M Pilowsky.

53 records · Page 3Linked to original sources
PubMed1990

Serotonin immunoreactive boutons make synapses with feline phrenic motoneurons.

In anesthetized cats, phrenic motoneurons were intracellularly labeled with HRP. Immunohistochemistry was used to localize serotonin-like immunoreactivity that was present in numerous boutons and nerve fibers within the ventral horn of the C5 spinal segment. Immunoreactive boutons were frequently found in apposition to phrenic motoneurons, but these close contacts were more common on the dendrites than the cell body. At the electron microscope level, serotonin-immunoreactive boutons were found to make synapses with well-defined postsynaptic densities on proximal and distal dendrites of phrenic motoneurons. These results suggest that serotonin-containing neurons may directly affect the excitability of phrenic motoneurons, mainly through an input onto their extensive dendritic trees.

Animals↗
PubMed1988

Central serotonergic mechanisms in hypertension.

Serotonin-containing neurons in the central nervous system are grouped into a number of discrete and distinctive collections with cell bodies in the brainstem and projections passing to many regions of the brain and spinal cord. Evidence is presented that activation of one projection of serotonin-containing neurons from the midbrain to the hypothalamus elevates arterial pressure. Evidence is also presented that activation of a projection descending from the lateral B3 serotonin cell group to the spinal cord elicits a pressor response that is accompanied by increased release of serotonin in the spinal cord and is independent of the C1 adrenaline-containing neurons that lie close by. In contradistinction, experiments are described demonstrating that activation of the midline group of B3 serotonin cells in the raphe nucleus causes a fall in arterial pressure, consistent with the view that different groups of serotonin neurons in the brain and spinal cord participate in the control of blood pressure in diverse ways and can have different effects on blood pressure. Finally, experiments are described showing that the hypotensive action of methyldopa is mediated in part through central serotonin nerves.

5,7-Dihydroxytryptamine↗
PubMed1988

N-methyl-D-aspartate receptors in the spinal cord mediate pressor responses to stimulation of the rostral ventrolateral medulla in the rat.

1. Activation of bulbospinal neurons projecting from the C1 area of the rostral ventrolateral medulla evokes a pressor response. The nature of the neurotransmitters involved in mediating this response at spinal cord level has not been established. 2. Amino acid antagonists were introduced into the spinal subarachnoid space to investigate the role of spinal amino acid receptors in mediating this pressor response in the anaesthetized rat. 3. Intrathecal administration of the amino acid receptor antagonists 2-amino-phosphono valeric acid (2APV), gamma-glutamyl glycine, kynurenate or glutamic acid diethylester (GDEE) attenuated the pressor responses to stimulation of the C1 area. These compounds have been shown to antagonize N-methyl-D-aspartate (NMDA) sensitive receptors. 4. Intrathecal administration of 2APV significantly attenuated the increase in blood pressure produced by injection of NMDA into the spinal subarachnoid space. 5. These results suggest that the pressor response produced by stimulation in the area of the C1 neurons in the rostral ventrolateral medulla of the rat is mediated at least in part by NMDA receptors in the spinal cord.

2-Amino-5-phosphonovalerate↗
PubMed1987

Inhibition of vasodepressor neurons in the caudal ventrolateral medulla of the rabbit increases both arterial pressure and the release of neuropeptide Y-like immunoreactivity from the spinal cord.

The role of bulbospinal neuropeptide Y (NPY)-containing neurons of the rostral ventrolateral medulla in the rabbit in mediating the increase in blood pressure that occurs during inhibition of cells in the caudal ventrolateral medulla was investigated in urethane-anaesthetized rabbits. In the present experiments bilateral injections of the GABA agonist, muscimol, into the caudal ventrolateral medulla elicited a slowly-developing rise in arterial pressure that was maximal 15 min after the injection. Accompanying this increase in arterial pressure was an increase in the release of NPY-like immunoreactivity (NPY-LI) into the spinal subarachnoid space. This pattern of response is similar to that seen after direct chemical stimulation of the NPY-containing cells of the rostral ventrolateral medulla. Taken together, these findings suggest that tonically active neurons in the caudal ventrolateral medulla exert their effects by inhibiting sympathoexcitatory NPY-containing neurons whose cell bodies are situated in the rostral ventrolateral medulla.

Animals↗
PubMed1987

Plasma atrial natriuretic peptide is increased during atrial pacing in conscious rabbits.

The effect of increases in heart rate on plasma atrial natriuretic peptide (ANP) concentrations was investigated in conscious rabbits. Plasma ANP concentrations were significantly increased following abrupt increases in heart rate produced by atrial pacing at 400 beats/min. Pacing at 300 beats/min resulted in smaller increases in plasma ANP concentration. Stepwise increases in heart rate produced by atrial pacing at 250, 300, 350 and 400 beats/min resulted in increases in plasma ANP concentrations at 400 beats/min only. The increase in plasma ANP concentration during atrial pacing correlated significantly with the increase in heart rate achieved.

Animals↗
PubMed1987

Microinjection of kainic acid into the rostral ventrolateral medulla causes hypertension and release of neuropeptide Y-like immunoreactivity from rabbit spinal cord.

Microinjections of kainic acid were made into the pressor area of the rostral ventrolateral medulla oblongata of anaesthetized rabbits, in the region of the C1 adrenaline-containing neurons. Over the 65 min following the microinjection, there was a significant increase in blood pressure, as well as an increase in the release of neuropeptide Y-like immunoreactivity into the spinal subarachnoid space. These data provide evidence for a functional bulbospinal neuropeptide Y-containing projection which may be responsible for mediating the pressor effects of stimulation of the rostral ventrolateral medulla.

Animals↗
PubMed1986

Spinal cord serotonin release and raised blood pressure after brainstem kainic acid injection.

The recently developed technique of in vivo dialysis has permitted us to make direct measurements of serotonin release in a specific region of the spinal cord and to relate this to changes in blood pressure elicited by chemical stimulation of the brainstem. In the present experiments we have shown that chemical stimulation of bulbospinal neurons in the region of the B3 cell group in the ventromedial medulla, causes an increase in the release of serotonin in the thoracic spinal cord and that this release is associated with an increase in blood pressure.

Animals↗
PubMed1986

Role of renal nerve activity, plasma catecholamines and plasma vasopressin in cardiovascular responses to intracisternal neurotoxins in the rabbit.

We have examined the acute (0-3 h) effect of intracisternally administered 5,7-dihydroxytryptamine (DHT) and 6-hydroxydopamine (6-OHDA) on blood pressure, heart rate, renal nerve activity, plasma adrenaline, plasma noradrenaline and plasma vasopressin in conscious rabbits. The increase in blood pressure seen following 5,7-DHT treatment was associated with increases in adrenaline and vasopressin levels and renal nerve activity throughout the response. The increase in blood pressure which followed 6-OHDA administration was associated with an increase in renal nerve activity alone. These findings indicate that the rise in blood pressure elicited by these drugs involves an increase in sympathetic nerve activity. The absence of a rise in vasopressin levels during the response to 6-OHDA suggests that the rise in blood pressure seen in these animals is due entirely to a bulbospinal sympathoexcitatory pathway.

5,6-Dihydroxytryptamine↗
PubMed1982

Acetylcholinesterase in neural tube defects: a model using chick embryo amniotic fluid.

Acetylcholinesterase was measured in amniotic fluid from normal chick embryos and embryos with neural tube defects. Neural tube defects were induced in the chick embryos by three procedures, removal of albumen, mechanical disruption of the closed neural tube or injection of tetanus toxin. The concentration of acetylcholinesterase in amniotic fluid from untreated normal embryos changed throughout the period examined (5-14 days incubation) but was stable at 0.5 U1(-1) over the time period 6-11 days. Amniotic fluid taken from treated embryos with neural tube defects at 8 days always contained a higher concentration of acetylcholinesterase than fluid from sham operated but otherwise normal embryos, mean 40.9 U1(-1), S.E.M. = 10. U1(-1), versus 1.0 U1(-1), S.E.M. = 0.2 U1(-1). The range of values (6.1-393 U1(-1)) was clearly separated from the normal values, range 0.0-5.5 U1(-1). In 13 cases with developmental abnormalities other than neural tube defects, the concentration of acetylcholinesterase was elevated in only one. Two different forms of acetylcholinesterase, as shown by gel electrophoresis, were present in fluid form both normal and defective embryos. These forms were also present in blood plasma, cerebrospinal fluid and in the high speed supernatant from brain extracts, the latter tissue contained an additional form of greater electrophoretic mobility. After irreversible inhibition, enzyme activity in amniotic fluid recovered slowly; only half the control value was reached by 140 h compared with complete recovery in the tissues of the embryo within 19 h. Histochemical staining for acetylcholinesterase showed that the spinal cord in the region of the lesion contained high concentrations of the enzyme. The possible sources of acetylcholinesterase in amniotic fluid are discussed. This chicken model of neural tube defects provides support for the use of acetylcholinesterase tests in the detection of neural tube defects clinically, and provides a model for experimentation with this system.

Acetylcholinesterase↗
PubMed1981

Combined analysis of acetylcholinesterase and alpha-fetoprotein improves the accuracy of antenatal diagnosis of neural-tube defects.

Acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and alpha-fetoprotein (AFP) were measured in 293 amniotic fluids from the second and third trimesters of pregnancy in a prospective study of their diagnostic value in the detection of neural-tube defects (NTD). In normal samples, the mean AChE and BChE concentrations were 3.0 u/L (SEM = 9.1 u/L) and 15.2 u/L (SEM = 1.2 u/L) in the second trimester, and 1.6 u/L (SEM = 0.1 u/L) and 7.8 u/L (SEM = 0.6 u/L) in the third trimester. AFP levels fell throughout the second trimester to unmeasurable levels in the third. AChE levels were markedly elevated in samples from NTD pregnancies at all gestational ages, and a cut-off level of the mean + 3 SD optimally separated normal from abnormal samples. This cut-off correctly predicted 10 of 11 fetuses with neural lesions; there were three false positive results. A similar cut-off for AFP predicted nine of 11 cases of neural lesion with two false positive results. For BChE, a cut off of 50 u/L predicted eight of 11 neural lesions with two false positive results. The specificity, sensitivity, and predictive value positive (PVP) were calculated for each test. The assays of AFP and AChE were useful when used individually (PVP congruent to 80%), but a Bayesian combination of these two tests produced a superior PVP (98%). Because the cost of AChE assay is low, and the test is so simple, it is suggested that an AChE analysis should be performed whenever an amniocentesis is requested for the diagnosis of NTD.

Acetylcholinesterase↗
PubMed1979

Acetylcholinesterase in human amniotic fluid: An index of fetal neural development?

Acetylcholinesterase (AChE) activity was detected in amniotic fluid either sampled by amniocentesis at 14--23 weeks gestation or collected at normal parturition. Activity ranged from 0.2 to 8.9 u/l in the earlier samples and from 0.2 to 4.2 u/l in the later samples. Since the fetal but not the maternal serum contained AChE activity, we suggest that the AChE in the amniotic fluid is derived from the fetus. AChE is released from both neural and nonneural tissues, and the release of the enzyme from both sources may diminish as the nervous system matures. The amount of AChE found in amniotic fluid may be affected by abnormalities of the nervous system. Amniotic fluid from two fetuses with spina bifida contained AChE activity: one, with a gestational age of 21 weeks, was in the upper levels of the normal range (4.5 u/l), whereas the other, at 36 weeks, contained 1.9 times more activity than the next highest sample. In a 20-week fetus with anencephaly, the AChE activity in the amniotic fluid was increased 2.8-fold over the activity of the highest "normal" sample.

Acetylcholinesterase↗
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↗