Chronic lability of arterial pressure produced by selective destruction of the catecholamine innervation of the nucleus tractus solitarii in the rat.
TL;DR: It is suggested that the catecholamine innervation of NTS modulates rather than mediates baroreceptor reflexes, serving to maintain arterial pressure within narrow limits.
Abstract: The effects of selective destruction of the catecholamine innervation of the nucleus tractus solitarii (NTS) on arterial pressure (MAP) and heart rate (HR) were examined in unanesthetized rats in which 6-hydroxydopamine (6-OHDA), 1μl, was injected bilaterally into the nucleus at the level of the obex. Control rats received 1 fil of vehicle or were uninjected. Baroreceptor reflex activity was tested by measuring the reflex bradycardia in response to graded doses of phenylephrine. 6-OHDA, 2 μg, did not alter MAP or HR; 12 μg, a dose producing necrosis of NTS, resulted in the development within 4-6 hours of fulminating arterial hypertension and tachycardia. 6-OHDA, 4 fig, produced an elevation of MAP which returned to control levels by 48 hours without changing HR. By 6 hours, however, the arterial pressure became extremely labile. Lability of MAP in the absence of hypertension or change of HR persisted for the longest period of observation, 2 weeks. Baroreceptor reflex activity remained, although the sensitivity of the reflex was depressed. 6-OHDA, 4 μg, failed to produce histological damage to NTS. Biochemically, it resulted after 14 days in a reduction of the activity of dopamine β-hydroxylase, a specific marker of noradrenergic and adrenergic neurons, to 40% of control without altering the activity of choline acetyltransferase, a marker of cholinergic neurons. We conclude that selective removal of a substantial portion of the catecholamine innervation of the NTS, mostly noradrenergic, results in persistent lability without elevation of arterial pressure. The results suggest that the catecholamine innervation of NTS modulates rather than mediates baroreceptor reflexes, serving to maintain arterial pressure within narrow limits.
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TL;DR: Electrolytic and ibotenic acid lesions of the LH demonstrate that neurons in the LH are involved in the autonomic, but not the behavioral, conditioned response pathway, whereas neurons inThe caudal CG are involvedIn the behavioral and autonomic pathway, although different efferent projections of the central amygdala thus appear to mediate the behavioraland autonomic concomitants of conditioned fear.
Abstract: The purpose of the present study was to determine whether lesions of areas projected to by the central amygdaloid nucleus (ACE) would disrupt the classical conditioning of autonomic and/or behavioral emotional responses. The areas studied included 3 projection targets of the ACE: the lateral hypothalamic area (LH), midbrain central gray (CG) region, and bed nucleus of the stria terminalis (BNST). Lesions were made either electrolytically or by microinjection of ibotenic acid, which destroys local neurons without interrupting fibers of passage. Two weeks later, the animals were classically conditioned by pairing an acoustic stimulus with footshock. The next day, conditioned changes in autonomic activity (increases in arterial pressure) and emotional behavior ("freezing," or the arrest of somatomotor activity) evoked by the acoustic conditioned stimulus (CS) were measured during extinction trials. Electrolytic and ibotenic acid lesions of the LH interfered with the conditioned arterial pressure response, but did not affect conditioned freezing. Electrolytic lesions of the rostral CG disrupted conditioned freezing but not conditioned changes in arterial pressure. Ibotenic acid injected into the rostral CG reduced neither the arterial pressure nor the freezing response. Injection of ibotenic acid in the caudal CG, like electrolytic lesions of the rostral CG, disrupted the freezing, but not the arterial pressure response. Injection of ibotenic acid into the BNST had no effect on either response. These data demonstrate that neurons in the LH are involved in the autonomic, but not the behavioral, conditioned response pathway, whereas neurons in the caudal CG are involved in the behavioral, but not the autonomic, pathway. Different efferent projections of the central amygdala thus appear to mediate the behavioral and autonomic concomitants of conditioned fear.
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TL;DR: According to this data, arterial pressure is elevated during restraint in SAD rats because buffering by the baroreceptor reflex is absent, and pressure measurements made under these conditions give a false indication of hypertension.
Abstract: The mean arterial pressure (MAP) of nine sinoaortic denervated (SAD) and eight control rats housed in standard-sized metabolic cages was determined continuously via aortic cannulae and computerized data collection over 24 hours. These continuous measurements were compared with direct, mean aortic pressure measurements and indirect, tail-cuff systolic pressure determinations made while these rats were resting in a Lucite restrainer. Denervated rats were studied 1 month after debuffering. Both types of measurements made during restraint indicated that the SAD rats were hypertensive; the MAP averaged 145 +/- 3.4 mm Hg (mean +/- SEM) in SAD rats compared with 119 +/- 2.8 mm Hg in the control group (p less than 0.001), and the tail-cuff pressure in SAD rats was 156 +/- 5.4 vs 121 +/- 2.7 mm Hg in control rats (p less than 0.001). In contrast, continuous monitoring showed that the SAD rats were normotensive; the MAP averaged 119 +/- 4.7 mm Hg in the SAD group and 119 +/- 3.1 mm Hg in the control group. Denervation increased pressure lability; the average 24-hour standard deviation of MAP was 19.0 +/- 1.2 mm Hg in SAD rats vs 8.0 +/- 0.7 mm Hg in control rats (p less than 0.001). Apparently, arterial pressure is elevated during restraint in SAD rats because buffering by the baroreceptor reflex is absent, and pressure measurements made under these conditions give a false indication of hypertension.
187 citations
TL;DR: It is proposed that C1 neurons comprise the so-called tonic vasomotor center of the brain stem and also mediate, via a projection from the NTS, the vasodepressor limb of baroreflexes.
Abstract: Neurons of the lower brain stem maintain resting levels of arterial pressure (AP), mediate reflex responses from cardiopulmonary receptors, and are an important site of the hypotensive actions of alpha 2-adrenergic agonists. Details of the pathways and transmitters that mediate tonic and reflex control of AP are emerging. Afferent fibers of cardiopulmonary receptors in the ninth and tenth nerves terminate bilaterally in the nucleus of the tractus solitarius (NTS). Although some neurons contain substance P, the primary neurotransmitter appears to be the excitatory amino acid L-glutamate (L-glu). Neurons in rostral ventrolateral medulla, which most probably comprise the C1 group of epinephrine neurons, are also critical in AP control. C1 neurons project to innervate cholinergic preganglionic sympathetic neurons in the spinal cord. Stimulation of the C1 area electrically or with L-glu increases AP, while lesions or local injection of the inhibitory amino acid gamma-aminobutyric acid (GABA) lowers AP to levels comparable to spinal cord transection. Lesions of C1 neurons or their pathways abolish vasodepressor reflexes from baroreceptors and vagal afferents. In contrast, noradrenergic neurons of the caudal ventrolateral medulla, the A1 group, project rostrally to innervate, in part, vasopressin neurons of the hypothalamus. Stimulation of A1 neurons lowers AP, while lesions or GABA elevates it. We propose that C1 neurons comprise the so-called tonic vasomotor center of the brain stem and also mediate, via a projection from the NTS, the vasodepressor limb of baroreflexes. The NTS-C1 projection may be GABAergic.
153 citations
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4,814 citations
"Chronic lability of arterial pressu..." refers background in this paper
...The NTS and adjacent regions of the dorsal medulla are richly innervated by catecholaminecontaining neurons.(8)"(11) It has been presumed on the basis of histofluorescence that most of the catecholamine-containing fibers innervating NTS are...
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...Third, the enzyme might be contained in the relatively few cell bodies of noradrenergic neurons which reside in the area of the NTS in rat.(8)"(11) The noradrenergic cell bodies are reputedly more resistant to the toxic action of the drug than are the terminals....
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TL;DR: The chest walls of rabbits exposed to steep-fronted air shock waves of short duration produced by 50 g spherical charges of TNT were recorded by means of a mechano-electric motion transducer to study the correlation between the deformations of the chest and the damage inflicted to the underlying organs, especially the lungs.
Abstract: The movements of the chest walls of rabbits exposed to steep-fronted air shock waves of short duration produced by 50 g spherical charges of TNT were recorded by means of a mechano-electric motion transducer originally developed for this investigation. The main purpose has been to study the correlation between the deformations of the chest and the damage inflicted to the underlying organs, especially the lungs. The motion parameters, amplitude, velocity and acceleration of the chest wall, were correlated to the physical characteristics of the shock wave as well as to the lung injury produced. The lung injuries were found to be highly correlated to the impulse of the incident shock wave, and also, although to a lesser degree, to the maximum overpressure of the shock wave, and to the velocity and acceleration acquired by the chest wall. The correlation of the lung injuries to the maximum amplitude of the inward displacement of the chest wall, on the other hand, was found to be much lower or even uncertain. The following critical values of the motion parameters were established. If the chest wall receives an impulse load of such a strength and duration that an inward relative movement results with a velocity of more than 15 m se& attained within a period of time of 150–200 ps, i. e. involving accelerations of the order of 104g, there is a high probability that a severe lung injury will result. Corresponding maxi mum amplitudes of the displacement of the chest wall were 5 to 7 mm. The lower limit of effective reflection pressures and impulses causing severe lung injuries were 10 bar and 1.5 gf sec cm-2, respectively. The biomechanical events occurring in the exposed chest are discussed in some detail.
2,714 citations
1,712 citations
"Chronic lability of arterial pressu..." refers methods in this paper
...changes in the cardiovascular responses resulting from the administration of 6-OHDA was determined by the two-tailed Student's £-test.(25) Student's t-test was also used to determine significant changes in enzyme activity....
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TL;DR: A sensitive immunofluorescene technique was used to describe systematically the distribution of dopamine‐β‐hydroxylase (DBH)‐containing cell bodies, non‐terminal fiber pathways, and terminal fields in the brain of the male albino rat.
Abstract: A sensitive immunofluorescence technique was used to describe systematically the distrubution of dopamine-beta-hydroxylase (DBH)-containing cell bodies, non-terminal fiber pathways, and terminal fields in the brain of the male albino rat. DBH is the enzyme that catalyzes the conversion of dopamine to noradrenaline, and as such is useful as an anatomical marker for noradrenaline and possibly adrenaline neurons. The enzyme is not present in dopamine- or indolamine-containing neurons. Ten micron frozen sections (1-in 20 series) were prepared in the frontal, sagittal, and horizontal planes from the olfactory bulb to the upper cervical segments of the spinal cord; adjacent sections in each plane were stained for DBH and for cells (toluidine blue=azure II). An atlas consisting of 40 projection drawings of selected frontal sections illustrates the results of the investigation. DBH perikarya are confined to three groups in the pons and medulla: the well defined locus coeruleus, a more diffuse but continuous subcoeruleus group that arches through the pons and ventral medulla, and a third dorsal medullary group centered in the dorsal motor nucleus of the vagus. A single principal adrenergic fiber system distributes a great many of the axons from these neuron groups to a majority of nuclear areas in the brain. In the pons and medulla two components of the fiber system may be distinguished. A medullary branch may be followed from the posterior aspect of the subcoeruleus group dorsally and then anteriorly through the lateral tegmental field and ventral aspect of the vestibular complex to a position subjacent to the locus coeruleus, where it is joined by a subcoeruleus branch consisting of a large number of fibers coursing among cells along the length of the subcoeruleus group, and by fibers arising from the locus coeruleus. Anterior to the locus coeruleus the principal adrenergic bundle courses as a single fiber tract immediately ventrolateral to the central gray in the mesencephalon and in the zona incerta and substantia innominata in the diencephalon. At the level of the septal area separate bundles reach the cortex dorsally over the genu of the corpus calosum via the medial septal-diagonal band nuclei and the lateral septum and ventrally between the olfactory tubercle and caudate-putamen. In the medulla and pons adrenergic fibers undoubtedly course in both directions. Anterior to the most rostral pontine cell bodies, however, all fibers presumably ascend. Along the course of the bundle distinct branches emerge to innervate circumscribed terminal fields. In addition, certain regions of the brain such as the reticular formation and pontine gray receive diffuse DBH innervation derived from less clearly defined pathways. A small number of areas in the brain contain little or no detectable DBH. These include the caudate-putamen, nucleus accumbens, globus pallidus, olfactory tubercle, subthalamic nucleus, substantia nigra, pretectal area, third, fourth and sixth cranial verve nuclei, and the trapezoid body nucleus.
1,460 citations
"Chronic lability of arterial pressu..." refers background in this paper
...It is generally believed that the major extrinsic catecholamine innervation of NTS is derived from fibers arising from the so-called A2 neuronal group lying mainly in the region of the commissural nucleus.(9)' n Since these cells can be shown by histofluorescence to contain catecholamines,(8) and by immunocytochemistry to contain DBH(9) but not phenylethanolamine iV-methyltransferase,(12) it must be assumed, therefore, that the major innervation of NTS by A2 is noradrenergic....
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TL;DR: It is concluded that the baroreceptor reflex are can be rapidly reset, particularly during sleep, and the lower arterial pressures during sleep may be actively maintained in some subjects by increased baroreflex sensitivity.
Abstract: The control of arterial pressure during sleep was studied in 13 untreated, unsedated subjects aged 20 to 46, including 7 with hypertension. Arterial pressure was measured directly. A transient rise of arterial pressure up to 30 mm Hg was produced by the sudden intravenous injection of 0.25 to 2 µg of angiotensin. Linear plots were obtained in 10 of 13 subjects when the systolic pressures of successive pulses during the pressure rise were plotted against the pulse intervals which began the next beat. The relationship was disturbed by movement or arousal, and was better when pulse intervals falling in inspiration were discarded. The slope of the line (milliseconds of cardiac slowing per millimeter rise in systolic pressure) in the awake subject ranged from 2 to 15.5 msec/mm Hg, and from 4.5 to 28.9 during sleep. Reflex sensitivity was highest in dreaming sleep. In 7 of 10 subjects, baroreflex sensitivity increased significantly during sleep; in 6, the prevailing arterial pressure was inversely correlated wi...
1,297 citations
"Chronic lability of arterial pressu..." refers methods in this paper
...Baroreceptor reflex activity was examined in unanesthetized rats by a modification of the method of Smyth et al.(18) We measured the slope of the curve describing the magnitude of the reflex bradycardia elicited in response to elevations of arterial pressure produced by graded doses of phenylephrine (Winthrop)....
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