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P R Howe

Publications and source records attributed to P R Howe.

At least 73 records · Page 4Linked to original sources

Growth hormone releasing factor immunoreactivity in rat hypothalamus.

Neurones immunoreactive to antibodies against human pancreatic growth hormone releasing factor1-40 (hpGRF) were identified in the hypothalamus of the rat after pretreatment with colchicine. Reactive perikarya were concentrated in the arcuate nucleus and were also present around the anterior commissure. hpGRF immunoreactive fibres were observed in the median eminence and preoptic area where they tended to complement the distribution of somatostatin immunoreactive fibres. The distribution of GRF-immunoreactive perikarya in the rat hypothalamus is similar to that reported in monkey, and is consistent with other studies which suggest that neural mechanisms stimulatory for growth hormone secretion in the rat are situated in the medial basal hypothalamus.

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Brainstem PNMT neurons and experimental hypertension in the rat.

The number of phenylethanolamine-N-methyl transferase (PNMT) cells visualised with immunohistochemical techniques in the medulla oblongata is increased by 20% in 4 week old spontaneously hypertensive rats (SHR) and stroke prone spontaneously hypertensive rats (SHR-SP). This is associated with a 50% increase in the activity of PNMT and a significant rise in the amount of PNMT enzyme protein present in the medulla and spinal cord of both 4 weeks old and 4 months old SHR and SHR-SP. Since previous experiments had demonstrated that sinoaortic denervation also increased spinal cord PNMT activity we subjected normotensive Wistar Kyoto control rats (WKY) and hypertensive SHR and SHR-SP to denervation and measured the changes in blood pressure and in PNMT activity. Mean arterial pressure rose immediately after denervation in all 3 strains of rats, with much greater rises in the SHR and SHR-SP than in WKY, but the increase in pressure was only sustained in the normotensive WKY, in which it remained elevated throughout the one week observation period. In a similar way, denervation of the arterial baroreceptors increased the activity of PNMT in the medulla and spinal cord of normotensive WKY controls, confirming the results of previous studies but was not able to increase the already elevated PNMT levels in the SHR and SHR-SP any further in these two tissues. We suggest that there is good evidence that PNMT neurons contribute to the maintenance and elevation of arterial pressure in both the neurogenic and genetic models of hypertension. It also seems likely that the activity of descending spinal PNMT neurons is more important in the maintenance of a sustained increase in pressure than in the induction of a transient rise.

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Distribution of serotonin nerve cells in the rabbit brainstem.

Serotonin (5-HT)-containing nerve cells in the rabbit brain were visualized immunohistochemically and were mapped on photographs of coronal brain sections. The 5-HT cells extended from the caudal medulla oblongata to the rostral midbrain and were mostly clustered in groups resembling those found in the rat brainstem. However, there were several notable differences between the rabbit and the rat in the distribution of 5-HT nerve cells. In particular, there were fewer pontine 5-HT cells in the rabbit and the major 5-HT cell groups of the midbrain and the ventral medulla oblongata were spread further laterally than in the rat brain.

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A biochemical and immunohistochemical study of central serotonin nerves in rats with chronic thiamine deficiency.

An immunohistochemical and neurochemical investigation of central serotonin (5-HT) nerves was made in rats deprived of dietary thiamine at various stages of development. The classical symptoms of severe thiamine deficiency were produced in adult rats which had been maintained on a synthetic thiamine-free diet for 5-8 weeks and in young rats reared from birth to weaning by thiamine-deficient mothers. Offspring of rats which had been thiamine-deficient throughout pregnancy were also studied; there were no visible symptoms of thiamine deficiency in these rats after weaning. The number and distribution of 5-HT nerve cell bodies in the brainstem were compared in control and thiamine-deficient rats after visualizing the cells by immunofluorescence of endogenous 5-HT. 5-HT nerve terminals and axons were also compared in normal and deficient rats by immunofluorescence after loading with 5,7-dihydroxytryptamine. The immunohistochemical examination showed that central 5-HT nerves were not affected in any of the groups of thiamine-deficient rats studied. This was confirmed by measurements of tryptophan hydroxylase activity and 5-HT concentration in several brain regions. These results do not support earlier reports of a selective impairment of central 5-HT nerves in chronic diet-induced thiamine deficiency.

Aging↗

Evidence for a bulbospinal serotonergic pressor pathway in the rat brain.

The cardiovascular role of spinal serotonin (5-HT) neurones descending from 5-HT cells near the ventrolateral surface of the medulla oblongata was investigated by stimulating these cells in normal animals and in animals with selective chemical ablation of 5-HT nerves. These laterally placed 5-HT nerves fall within the B1 and B3 groups in the medulla and were identified using immunohistochemistry. 5,7-Dihydroxytryptamine (5,7-DHT) was injected into the lateral cerebral ventricle (i.c.v.) to produce a generalized destruction of central 5-HT pathways, with preliminary intraperitoneal administration of desipramine to prevent depletion of noradrenaline stores. In other experiments, 5,7-DHT was injected directly into the cervical spinal cord, after preliminary treatment with desipramine, to produce selective destruction of spinal 5-HT nerves, confirmed both biochemically and immunohistochemically. Electrical stimulation near the lateral 5-HT cells in the B1 and B3 cell groups elicited pressor responses in control (vehicle-injected) rats; the increase in mean arterial pressure was proportional to the intensity and to the frequency of stimulation. Microinjections of kainic acid or L-glutamate at the same sites also produced an increase in mean arterial pressure. Selective destruction of 5-HT nerves, whether produced by i.c.v. or intra-spinal administration of 5,7-DHT, reduced the magnitude of the pressor response to electrical stimulation by over 50%. These experiments suggest the activity of 5-HT nerve cells adjacent to the ventrolateral surface of the medulla oblongata and projecting to the intermediolateral cell column serves to elevate arterial pressure and maintain vasomotor tone.

5,7-Dihydroxytryptamine↗

Improved immunohistochemical visualization of central serotonin nerves after loading with 5,7-dihydroxytryptamine.

5,7-Dihydroxytryptamine (5,7-DHT), which reacts with a monoclonal antibody raised against 5-hydroxytryptamine (5-HT), has been used to increase the sensitivity of the immunohistochemical detection by this antibody of central 5-HT nerves in the rat brain. Rats pretreated with tricyclic antidepressants were given a single intraventricular injection of 5,7-DHT and were sacrificed 30 min-3 h later. This treatment resulted in accumulation of 5,7-DHT by central 5-HT nerves and selectively enhanced the immunofluorescence reaction of these nerves, particularly the terminals and non-terminal fibres.

5,7-Dihydroxytryptamine↗

Content and turnover of noradrenaline in spinal cord and cerebellum of spontaneously hypertensive and stroke-prone rats.

The concentration of noradrenaline was measured in various regions of the brain and spinal cord of spontaneously hypertensive rats, stroke-prone spontaneously hypertensive rats and normotensive Wistar/Kyoto controls. Elevated noradrenaline levels were consistently found in the pons, cerebellum and spinal cord of the two hypertensive strains. These changes occurred both in young rats, during the early development of hypertension, and in mature rats, after establishment of the hypertension. The increases of cerebellar and spinal noradrenaline in mature stroke-prone rats could not be reversed by lowering blood pressure with hydralazine. The increased noradrenaline concentrations were not accompanied by increased tyrosine hydroxylase activity in the hypertensive rats. However, comparisons of noradrenaline turnover made using the catecholamine synthesis inhibitor, alpha-methyltyrosine, indicate an increased turnover of spinal noradrenaline in both hypertensive strains after establishment of hypertension. The results suggest that the activity of spinal noradrenergic nerves is augmented in genetically hypertensive animals.

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Increased number of PNMT-immunofluorescent nerve cell bodies in the medulla oblongata of stroke-prone hypertensive rats.

An antiserum to bovine adrenal PNMT was used to identify PNMT-containing nerve cell bodies in the medulla oblongata of 4-week-old normotensive Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. The regional distribution of PNMT cells and the total number of PNMT cell profiles in tranverse sections of the medulla were examined in each of the two strains. While there was no significant difference in the pattern of distribution of the cells, both the number of PNMT cell profiles per section and the total number seen in all sections of the medulla were significantly higher in the hypertensive rats. The increase in counts of PNMT cell profiles in the medulla suggests that there is a genetic difference in the number of central adrenaline neurons in these hypertensive rats. This is supported by the finding of similar increases of PNMT enzyme activity in the medulla of both stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats compared with Wistar-Kyoto rats.

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Adrenaline neurons and PNMT activity in the brain and spinal cord of genetically hypertensive rats and rats with DOCA--salt hypertension.

1. We have studied the number of phenylethanolamine-N-methyltransferase (PNMT)-containing nerve cells in the medulla and the activity of PNMT in the medulla, spinal cord and hypothalamus of the rat. 2. At 4 weeks of age there was an increase in the number of PNMT cells counted in the medulla of the spontaneously hypertensive rat (SHR; 21%, P less than 0.01) and the stroke-prone spontaneously hypertensive rat (SHR-SP; 22%, P less than 0.01) compared with the Wistar--Kyoto (WKY) control rat. 3. At 4 months of age there were no significant differences in the number of medullary PNMT cells in two normotensive strains (WKY and Fisher rats), two genetically hypertensive strains (SHR and SHR-SP) and in DOCA--salt hypertensive rats. 4. In four week old rats the activity of PNMT was increased by about 50% in the spinal cord and medulla of the SHR and SHR-SP compared with the WKY rats, and immunotitration experiments suggest that this is due to an increased concentration of enzyme. 5. At 4 months of age there were no increases in PNMT activity of either genetically hypertensive rats or DOCA--salt hypertensive rats.

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Altered cardiac noradrenaline stores in DOCA-salt hypertensive rats.

1. The storage of noradrenaline (NA) in hearts of DOCA-salt hypertensive rats was examined after in vivo administration of labelled NA. 2. The cardiac NA concentration and the neuronal NA storage capacity were reduced in these rats compared with normotensive controls. The extent of reduction was dependent on the duration of hypertension. 3. These findings are similar to observations on spontaneously hypertensive rats and support the hypothesis that storage of the cardiac sympathetic transmitter is impaired in DOCA-salt hypertension.

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Residual catecholamines in extrinsically denervated guinea-pig ileum.

1. Concentrations of noradrenaline, adrenaline and dopamine were measured in the submucosa and myenteric plexus of innervated and extrinsically denervated guinea-pig ileum using a sensitive radioisotope enzymatic assay for catecholamines. 2. Subcellular fractionation studies indicated that the microsomal fraction obtained from both layers of the normal ileum was greatly enriched with noradrenaline compared to the total homogenate. Low levels of adrenaline and dopamine were also detected in both layers of the ileum. 3. After extrinsic denervation or pretreatment with reserpine, noradrenaline was reduced to less than 3% and could no longer be visualized histochemically. Small proportions of the adrenaline and dopamine also disappeared after extrinsic denervation. 4. The residual amounts of noradrenaline, adrenaline and dopamine present after extrinsic denervation were not sensitive to reserpine and were not concentrated in microsomal fractions suggesting that these amines are not stored as neurotransmitters in intrinsic neurons of the intestine.

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Importance of new catecholamine pathways in control of blood pressure.

The first comprehensive maps of central catecholamine pathways referred to both noradrenaline and dopamine neurons. They described the catecholamine neurons as having their cell bodies in the brainstem with spinal axons descending mainly from two medullary cell groups (A1 and A2) and with ascending axons arising mainly from more rostral groups (A3-A13). More recent work utilising immunohistochemistry has established the presence of adrenaline neurons in the brain, in two medullary cell groups (C1 and C2). While these were originally thought to lie within the rostral part of the A1 and A2 cell groups, work from this laboratory has now established that the adrenaline neurons are topographically distinct from the A1 and A2 cells, do not fluoresce with standard methods, and are collected into three groups, the third group (C3) lying in the midline of the rostral medulla. Work in this laboratory using a combination of histochemical fluorescence and retrograde transport of horseradish peroxidase has demonstrated that existence of a descending dopaminergic projection from the hypothalamus to the spinal cord, indicating that descending pathways can arise well above the medulla. Recent studies on the A1 neurons have established the presence of projections from the A1 cells to the median eminence of the hypothalamus and towards the nucleus tractus solitarius in the medulla. Other experiments have demonstrated that most of the descending catecholamine axons do not arise from the A1 and A2 cell groups in the caudal medulla, but higher up in the brainstem especially from the A5 and A7 cell groups. These new descriptions of central catecholamine neurons will necessarily modify the interpretation of many experiments on the central regulation of arterial pressure.

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