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A D Loewy

Publications and source records attributed to A D Loewy.

At least 73 records · Page 4Linked to original sources

Topographic organization of substance P and monoamine cells in the ventral medulla of the cat.

A topographic map of the substance P and monoamine neurons in the ventrolateral medulla of the cat has been constructed from peroxidase anti-peroxidase immunohistochemically stained sections. The coordinates of this map use the foramen cecum of the medulla oblongata (i.e. the triangular depression at the junction between the caudal boundary of the pons and the rostral limit of the median fissure between the pyramidal tracts) as the zero point. Two distinct groups of substance P neurons have been found: a rostral group lies ventral to the facial nucleus and a caudal one is found ventrolateral to the inferior olivary nucleus. Two dopamine beta-hydroxylase-containing cell groups were identified that correspond to the A1 and A5 cell groups. The A5 cell group lies dorsal, lateral and caudal to superior olivary nucleus. The A1 cell group lies approximately 4.0-5.0 mm lateral to the midline at the level of the inferior olive; these cells lie mainly dorsolateral to the region of the magnocellular division of the lateral reticular nucleus. The B1 and B3 serotonin (5-hydroxytryptamine) cell groups of the ventrolateral medulla appear to form a continuous column with a rostral and a caudal swelling. The rostral group begins at the level of the facial nucleus (approximately 4 mm caudal to the foramen cecum) and is concentrated in the area just lateral to the pyramidal tract. It becomes reduced in size approximately 8.0 mm caudal to the foramen cecum, and then enlarges to form a caudal group (approximately 10 mm caudal to foramen cecum). Portions of this column overlap with the caudal substance P cell group. The C1 cell group lies in a restricted zone approximately 4.0 mm lateral to the midline at the level of the rostral part of the inferior olivary nucleus.

Animals↗

Comparative vascular pharmacology of the atriopeptins.

The atriopeptins are potent relaxants of norepinephrine-constricted aortic strips or are dilators of renal blood vessels in isolated perfused rat kidneys that are constricted by norepinephrine. This vasorelaxant property of the atriopeptins requires the presence of phenylalanine arginine (i.e., atriopeptin II, III, or ser-leu-arg-arg atriopeptin III) residues in the carboxy terminus which are considerably more effective than atriopeptin I (the 21 amino acid peptide which lacks the phe-arg C-terminus) or the core peptide (residues 3-19). However, these artificially in vitro precontracted preparations do not accurately predict the vascular effectiveness of the atriopeptins in intact rats. Intravenous administration of the atriopeptins (including atriopeptin I) to anesthetized rats produces concentration-dependent hypotension, a selective decrease in renal resistance in low doses (determined with microspheres), and pronounced diuresis. At higher doses, atriopeptins increase blood flow in other vascular beds. On the other hand, in the anesthetized dog, injection (intraarterially) of the phe-arg-containing peptides produces a concentration-dependent increase in both renal blood flow and sodium excretion, whereas atriopeptin I is inactive. Although there is a species difference in responsiveness to atriopeptin I, these data demonstrate a direct correlation between the renal vasodilation and diuresis produced by this novel family of atrial peptides.

Animals↗

Projections from the ventral respiratory group to phrenic and intercostal motoneurons in cat: an autoradiographic study.

Anterograde transport of tritiated amino acids (leucine, lysine, and proline) was used to examine the spinal projections of respiratory premotor neurons in the ventral respiratory group (VRG) of cats. This population of neurons corresponds anatomically with the nucleus ambiguus-retroambigualis. Small volumes (20 to 50 nl) of tritiated amino acids were pressure ejected into the middle of the VRG through a micropipette which permitted simultaneous recording of respiratory modulated activity. In two cats injections were made caudal to the obex in regions which contained expiratory modulated neurons. In five cats injections were made rostral to the obex in regions containing inspiratory neurons. After a 2-week survival period, cats were anesthetized and perfused. The entire neuraxis was removed and processed using standard autoradiographic techniques. Transport of tritiated amino acids revealed a marked bilateral projection to lamina IX of the spinal cord at the C4 to C6 level and a primarily contralateral projection to laminae VIII and IX in the thoracic spinal cord. Distinct descending pathways to the phrenic motor neurons were observed in the lateral funiculus and in the ventral funiculus; descending fibers to the intercostal motoneurons in the thoracic cord appeared to be restricted to the ventral funiculus. Labeling of axon terminals in both the cervical and thoracic cords was confined to ventral horn regions which contain motoneurons. These results suggest that monosynaptic projections from brainstem bulbo-spinal neurons to spinal motoneurons are important in controlling respiratory movements of the diaphragm and intercostal muscles.

Animals↗

[3H]substance P binding in the intermediolateral cell column and striatum of the rat.

[3H]substance P binding was studied in the intermediolateral cell column and striatum in the rat using slide-mounted sections. The intermediolateral cell column had a single high affinity binding component with a dissociation constant, Kd = 1.45 nM and the number of sites, Bmax = 18.1 fmol per mg protein. The striatum had a Kd = 0.77 nM and a Bmax = 23.5 fmol per mg protein. The relative potency of various substance P-like tachykinins in displacing [3H]substance P suggested that both these areas may contain a substance P-P (for physalaemin) receptor subtype. (D-Pro4, D-Trp7,9)substance P(4-11), a substance P antagonist, has a relatively low affinity (micromolar range) in both these areas.

Animals↗

GABA antagonists applied to the ventral surface of the medulla oblongata block the baroreceptor reflex.

Application of gamma-aminobutyric acid (GABA) antagonist drugs (bicuculline, picrotoxinin) to the intermediate region of the ventral surface of the medulla oblongata of gallamine paralyzed, alpha-chloralose anesthetized cats produced a dose-dependent blockade of the baroreceptor reflex. GABA antagonists applied to the rostral and caudal areas did not block the baroreceptor reflex. When strychnine was applied to the ventral medulla, it did not block the baroreceptor reflex. The diffusion of [3H]bicuculline was studied by scintillation counting and autoradiography and found not to penetrate more than 2 mm from the ventral medullary surface. These results suggest that a GABAergic synapse lies within the first 2 mm of the ventral medulla and is involved in baroreceptor modulation of the sympathetic outflow.

Animals↗

Substance P immunoreactivity released from rat spinal cord after kainic acid excitation of the ventral medulla oblongata: a correlation with increases in blood pressure.

Kainic acid injections into the ventral medulla oblongata of sodium pentobarbital-anesthetized rats caused an almost immediate increase in mean arterial pressure which reached hypertensive levels (greater than 200 mm Hg). Correlated with this rise in blood pressure was a two-fold increase in the amount of SP-like immunoreactivity (SPLI) in spinal cord superfusion samples. Baseline values obtained from a pool of two rats went from approximately 10 pg/10 min to approximately 20 pg/10 min. Rats pretreated with intracerebroventricular injections of the serotonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), were also given kainic acid injections into the ventral medulla. 5,7-DHT did not block pressure response to kainic acid nor the elevation of SPLI in spinal cord superfusates. However, baseline levels of SPLI were decreased by approximately 50% in 5,7-DHT-treated rats. These findings show that activation of the ventral medulla oblongata causes an elevation of SPLI in spinal cord superfusates concomitant with an elevation in mean arterial blood pressure. These responses appear to be independent of serotonergic systems.

5,7-Dihydroxytryptamine↗

Changes in regional blood flow and cardiac output after L-glutamate stimulation of A5 cell group.

Changes in regional blood flow and cardiac output were measured by the reference organ method in pentobarbital-anesthetized rats with radioactive microspheres (15 microns) before and after chemical stimulation of the A5 cell group with the excitatory amino acid L-glutamate an agent that excites cell bodies but not fibers of passage. This stimulation caused a decrease in mean arterial pressure, heart rate, cardiac output, and calculated stroke volume. The limb skeletal muscles showed a large increase in blood flow and decrease in vascular resistance, whereas the trunk musculature showed no change in flow or resistance. The blood flow of the entire gastrointestinal tract decreased. Blood flow in the skin decreased with no change in resistance. The cardiac muscle of the ventricles showed a decrease in flow without a change in resistance. The ipsilateral half of the brain showed a decrease in blood flow, while the contralateral side showed no change. The kidneys exhibited no change in blood flow and a decrease in resistance. A5 stimulation in guanethidine-sympathectomized rats caused no change in regional blood flow. In contrast, an increase in cardiac output was observed, and the possible interpretations for this change are discussed. Rats treated with intraventricular injections of 6-hydroxydopamine showed no changes in regional blood flow or cardiac output, indicating that catecholamine neurons are involved in these responses.

Animals↗

Projections of the pedunculopontine tegmental nucleus in the rat: evidence for additional extrapyramidal circuitry.

The projections of the pedunculopontine tegmental nucleus (PPT) were studied in the rat using anterograde and retrograde transport methods. Ascending fibers to the substantia nigra, the subthalamic nucleus, the globus pallidus, the entopeduncular nucleus, the neostriatum, the ventral thalamus, and the medial and sulcal frontal cortical areas were identified. PPT has been reported to receive afferents from the substantia nigra, the subthalamic nucleus, the entopeduncular nucleus and the neostriatum. The connections of PPT provide an additional limb to extrapyramidal circuitry.

Afferent Pathways↗

Actions of N-methyl aspartate and its antagonist aminophosphonovalerate on the A5 catecholamine cell group in rat.

When N-methyl-D,L-aspartic acid was injected into the A5 catecholamine cell group of the rat, a dose-dependent decrease in blood pressure and heart rate was obtained. These cardiovascular changes were subsequently blocked by the (-) and (+) isomers of the aspartate receptor blocker 2-amino-5-phosphonovalerate (2-amino-5-phosphonopentanoic acid). The (-) isomer was 2-4 times more potent than the (+) form.

2-Amino-5-phosphonovalerate↗

Substance P antagonist inhibits vasomotor responses elicited from ventral medulla in rat.

Application of kainic acid to the ventral medulla in rats leads to increases in blood pressure and heart rate. These responses can be attenuated or reversed by infusion of the substance P antagonist--(D-Pro2,D-Trp7,9)-substance P into the spinal subarachnoid space. Kainic acid elicits normal pressor responses from rats that have been treated intracisternally with the serotonin neurotoxin 5,7-dihydroxytryptamine. These results suggest that the substance P-like neurons of the ventral medulla may play a role in maintaining vasomotor tone.

Animals↗

Substance P neurons project from the ventral medulla to the intermediolateral cell column and ventral horn in the rat.

The descending substance P projections from the ventral medulla were studied in the rat. Electrolytic lesions which included the nucleus interfascicularis hypoglossi decreased the substance P-like immunoreactivity (SP-I) in both the intermediolateral cell column and the ventral horn of the spinal cord. Lesions of other ventral medullary areas and midbrain hemisections did not change spinal cord SP-I levels. Intracerebroventricular administration of the serotonin neurotoxin, 5,7-dihydroxytryptamine, reduced the SP-I content of the ventral horn but not of the intermediolateral cell column.

5,7-Dihydroxytryptamine↗

Efferent projections of the A1 catecholamine cell group in the rat: an autoradiographic study.

Efferent connections of the region of the A1 catecholamine cell group were investigated by the anterograde autoradiographic method in rats, some of which had been pretreated with intraventricular injections of 6-hydroxydopamine (6-OHDA). Spinal projections were further studied by combining histofluorescence and horseradish peroxidase staining in the same sections. Projections from the A1 region ascend through the lateral hypothalamus to the bed nucleus of the stria terminalis, the medial preoptic area, and several hypothalamic nuclei: the dorsomedial nucleus, the dorsal hypothalamic area, the paraventricular and supraoptic nuclei, and the median eminence. These projections are predominantly ipsilateral. Since they are sensitive to 6-OHDA, they presumably arise from catecholamine cells of the A1 group. Other pathways are not noticeably affected by 6-OHDA. These include projections through the reticular formation to the contralateral nucleus ambiguus, the ipsilateral facial nucleus, and the Kölliker-Fuse nuclei, the parabrachial nuclei and the periaqueductal gray on both sides, as well as the intralaminar nuclei of the thalamus. These pathways probably do not arise from the A1 group, although a minor noradrenergic component cannot be ruled out. Spinal projections extend to the intermediolateral cell column and the ventral horn, and especially to the phrenic motor nucleus. However, these projections arise almost exclusively from non-catecholamine cells. Only a small minority of the fluorescent A1 cells are retrogradely labeled after injections of HRP into the upper thoracic spinal cord. They lie at the level of the pyramidal decussation. Likewise only a few fluorescent cells of the A2 group are labeled. Although the A1 and A2 groups were long thought to be principal sources of spinal norepinephrine, a review of the literature shows that this belief was based on equivocal evidence.

Amino Acids↗

Effects of kainic acid applied to the ventral surface of the medulla oblongata on vasomotor tone, the baroreceptor reflex and hypothalamic autonomic responses.

Application of an excitotoxic amino acid, kainic acid, to the ventral medullary surface just caudal to the trapezoid bodies (at Feldberg and Guertzenstein's glycine-sensitive area) led to the following observations. (1) Blood pressure began to rise within 25 s and by 10 min rose to high levels (200-240 mm Hg). Blood pressure subsequently fell to levels at or approaching those of a spinal animal. (2) Sympathetic vasomotor activity became insensitive to baroreceptor inhibition shortly after the peak in blood pressure, and the cardioinhibitory action of the reflex was enhanced during this time. (3) The autonomic effects of hypothalamic stimulation were differentially affected--pupillary dilatation and retraction of the nictitating membranes were unaffected, while the increases in blood pressure and renal nerve activity were blocked. (4) Recovery from these effects was observed on two occasions, when the animals were infused with a pressor agent and allowed to survive beyond 6 h after the kainic acid application. These results support the view that vasomotor tone is dependent upon the activity of relatively superficial cells in the ventral medulla. We further suggest that baroreceptor inhibition of sympathetic vasomotor activity acts via these cells and that descending hypothalamic autonomic pathways are organized at this level in terms of separate end organs.

Animals↗

The distribution of glutamate, GABA and aspartate in the nucleus tractus solitarius of the cat.

This report describes the distribution of glutamate, GABA and aspartate in the nucleus tractus solitarius (NTS), area postrema, dorsal vagal nucleus and hypoglossal nucleus. Glutamate levels were particularly high in the dorsal, medial and commissural nuclei of the NTS. Section of the IXth and Xth cranial nerves caused a bilateral decrease in glutamate (ipsilateral side = 48%; contralateral side = 36%) and ipsilateral decrease in GABA (27%) in the dorsal and medial NTS. The ipsilateral dorsal vagal nucleus showed a 48% decrease in glutamate and a 30% decrease in GABA after axotomy.

Animals↗

Raphe pallidus and raphe obscurus projections to the intermediolateral cell column in the rat.

The descending spinal projections from the raphe pallidus and raphe obscurus nuclei were studied by the anterograde autoradiographic technique in the rat. Both regions project to the intermediolateral cell columns. These pathways were destroyed by intraventricular injections of 5,7-dihydroxytryptamine, a neurotoxin relatively specific for serotonergic cells.

5,7-Dihydroxytryptamine↗