Carotid Body Removal Research Articles

BDNF Supports Mammalian Chemoafferent Neurons in Vitro and Following Peripheral Target Removal in Vivo

Chemoreceptor neurons innervating the rat carotid body were used as a model system to define target regulation of visceral sensory development in fetal and newborn animals. In vitro, chemoafferents were selectively supported by coculture with the carotid body or by treatment with trkB ligands [brain-derived neurotrophic factor (BDNF) and neurotrophin-4], whereas nerve growth factor and neurotrophin 3 had no effect. In vivo, chemoafferent neurons died following carotid body removal at birth, indicating a predominant role of peripheral, rather than central, targets in mediating survival at this stage. However, in the absence of target tissues, a large proportion of carotid body afferents could be rescued by implants containing BDNF. Moreover, BDNF mRNA was detected in the newborn carotid body by reverse transcriptase polymerase chain reaction. These data provide the first demonstration that BDNF can substitute for peripheral target support of sensory neuron survival in vivo and indicate that trkB ligands may be particularly important for development of visceral afferents involved in cardiorespiratory control.

Physiological chemoreceptor stimulation decreases enkephalin and substance P in the carotid body

Neuroactive peptides, including the enkephalins (Met- and Leu-enkephalin; ME, LE) and substance P (SP) are known to be present in the mammalian carotid body, an arterial chemoreceptor organ sensitive to the O 2, CO 2 and pH levels in blood. The principal parenchymal (type I) cells of the organ, which receive sensory innervation from the carotid sinus nerve (CSN), have been shown to contain both ME and SP; SP is also present in CSN afferent fibers. In the present study, rabbits were exposed in a chamber to a physiological chemoreceptor stimulus (5% O 2 in N 2) for one hour, then anesthetized during surgical removal of both carotid bodies for later RIA measurement of ME and SP levels in the tissue; control animals were exposed to air in the chamber, but otherwise treated as the hypoxic animals. Both ME and SP levels were significantly reduced (approximately 40%) in the carotid bodies from hypoxic rabbits, compared to their normoxic controls. The results suggest that these neuroactive peptides are released from carotid body elements during physiological stimulation, and consequently may play a role in the transduction of chemosensory information between the type I cells and their apposed afferent terminals.

Ventilation in intact and glossopharyngeal nerve sectioned anaesthetized rats exposed to oxygen at high pressure.

The cause of the initial hyperventilation, which occurs on exposure to O2 at high pressure (o.h.p.), has been investigated by measuring tidal volume (VT), frequency of breathing (f) and hence ventilation (VE) in thirty-six barbiturate-anaesthetized rats, with or without their glossopharyngeal (IX) nerves sectioned, during 30-60 min of exposure to o.h.p. at 4, 6 or 8 atm absolute. In intact rats the rates of rise of VT, f and VE with time during exposure to o.h.p. were smallest at 4 and greatest at 8 atm absolute. In IX-sectioned rats the rates of rise of VT at 4, 6 and 8 atm absolute and of f at 4 atm absolute were similar to those of intact rats. At 6 atm absolute and even more so at 8 atm absolute, however, f decreased. Hence the slope of VE in IX-sectioned compared with intact rats was similar at 4 atm absolute but smaller at 6 and 8 atm absolute. In fact at 8 atm absolute VE remained constant in IX-sectioned rats. Since the slope of VE versus time in intact rats was steeper the greater the pressure and since the removal of carotid bodies in IX-sectioned rats reduced the VE slope at 6 and 8 atm absolute, the stimulus to the hyperventilation induced by o.h.p. cannot be an accumulation of CO2 in the brain resulting from the lack of O2 desaturation of haemoglobin. This theory would predict that VE should be identical at all pressures above 3.5 atm absolute. The findings in the IX-sectioned rats indicate a major contribution of the carotid bodies to the f increase in o.h.p. They may be stimulated by a histotoxic hypoxia induced by early O2 poisoning. Since the VT increase on exposure to o.h.p. was both large and fairly similar in intact and IX-sectioned rats, it is suggested that a large part of the VT increase was caused by stimulation of the central chemoreceptors by lactic acidosis induced by an o.h.p.-induced histotoxic hypoxia of the brain.

Loss of peripheral chemoreflexes to hypoxia after carotid body removal in the rat

Young Sprague-Dawley female rats (16–18 days old) were subjected to bilateral carotid glomectomy or the sham operation under halothane anaesthesia. After recovery, the rats were placed with non-operated peers. One to six months later glomectomised, sham-operated and control animals were anaesthetized with sodium pentobarbital. Respiratory minute volume and arterial pressure were recorded. Respiratory responses to few-breath administration of oxygen or nitrogen, and arterial pressure responses to carotid occlusion or tugging were tested. Oxygen produced transient hypoventilation and nitrogen transient hyperventilation in control, sham and 3 of 31 glomectomised rats. Bilateral vagotomy did not abolish these responses. In only those 3 glomectomised rats was carotid glomus tissue histologically identifiable. Carotid occlusion raised and tugging lowered arterial pressure in all animals. Glomectomy did not affect serum levels of GH, FSH, LH or PRL hormones but produced right ventricular hypertrophy. We conclude that peripheral chemoreception requires the presence of glomus tissue.

Restoration of reflex ventilatory response to hypoxia after removal of carotid bodies in the cat

In mammals there are two sets of peripheral arterial chemoreceptors, the carotid bodies innervated by the sinus branch of the glossopharyngeal nerve and the aortic bodies innervated by the vagus nerves. The afferent impulse discharge from both receptors increases during hypoxia and there is a reflexly mediated increase in ventilation (hypoxic hyperventilation). In the present study we tested this response by exposing anesthetized cats to decreased inspired O 2 concentration before and up to 315 days after bilateral resection of the carotid bodies. Acutely after removing the carotid bodies, hypoxic hyperventilation was abolished. This observation supports the view that the reflex pathway from the aortic body receptors normally contributes minimally to hypoxic hyperventilation. Subsequently, there was a restoration of hypoxic hyperventilation. Restoration was significant 30–43 days after removing the carotid bodies, it reached 70% of the preoperative value at 93–111 days and was essentially complete in terminal experiments 260–315 days after carotid body resection. In terminal experiments, hypoxic hyperventilation was not affected by recutting the regenerated carotid sinus nerves but was abolished completely by bilateral transection of the cervical vagosympathetic trunks. The restored ventilatory response was due predominantly to an increase in rate of breathing while an increase in tidal volume was predominant before carotid body resection. Resting ventilation breathing room air was not consistently decreased after carotid body resection while expired CO 2 was elevated from day 20 to day 111 and at the preoperative level in terminal experiments. It is concluded that restoration of hypoxic hyperventilation in the cat after carotid body resection is mediated by the reflex pathway from aortic body chemoreceptors. The possible contribution of chemo-receptive regenerated carotid sinus nerve axons was excluded. It is suggested that restoration may be a consequence of the central reorganization of chemoreceptor afferent pathways consequent to interruption of the carotid body reflex pathway and that as a result the ‘gain’ of the aortic body ventilatory chemoreflex is enhanced.

Erythropoiesis in Carotid Body Resected Cats

Abstract It has been reported that removal of carotid bodies in cats results in a brief, profuse reticulocytosis followed by depression to below-normal levels of reticulocytes and a progressively severe anemia. Injection of cat carotid body extract was reported to increase erythrocyte 59Fe incorporation in polycythemic rats. Other studies could find no hematological abnormality in humans after bilateral carotid body resection. We reexamined the effect of carotid body resection in the cat with serial bone marrow aspirations, hematocrit determination, and reticulocyte determination. T1/2 for plasma 59Fe removal, erythrocyte 59Fe incorporation, and 51Cr lifespan determinations were performed on five operated and three control cats. No significant differences were found. We conclude that the carotid body has no direct effect on erythropoiesis and that the anemia reported in a prior study was secondary to sepsis resulting from an indwelling femoral vein catheter.

Carotid body: structure and function.

Through an unfortunate error in make-up of the article “Carotid Body: Structure and Function,” by T. J. Biscoe, in the July issue of this journal, two sections of the review are out of order. To co...

The carotid body as a neuroendocrine organ involved in control of erythropoiesis.

The carotid body is generally regarded solely as a chemoreceptor. This paper presents evidence that the carotid body is also an endocrine gland, secreting one or more erythropoiesis-controlling hormones. Its removal is followed by anemia and by a lack of reticulocyte response to daily bleeding. The removal of both carotid bodies results in a reduction of the high reticulocyte count induced by daily bleeding (5-40% of erythrocytes) down to 0.1% of erythrocytes. The injection of an extract of the carotid body causes reticulocytosis within 5 hr. This reticulocytosis attains its peak 48-72 hr after injection. Daily bleeding for 15 days produces an increase in weight of the carotid body and ultrastructural alterations that indicate increased protein synthesis in the main cells. The injection of plasma from efferent blood from the carotid body into either normal cats or cats from which both carotid bodies have been removed is followed within 6 hr by the appearance of large numbers of reticulocytes and macroreticulocytes in peripheral blood. Carotid body extracts and efferent blood plasma exhibited erythropoietin activity, which was demonstrated in the polycythemic rat by the (59)Fe incorporation method.

The central depressant profile of carbamate ester of glycerol ether: 3-(1,2,3,4-tetrahydro-7-naphthyloxy)-2-hydroxypropyl carbamate

The general pharmacologic and toxicologic characteristics of a new central depressant compound, 3-(1,2,3,4-tetrahydro-7-naphthyloxy)-2-hydroxypropyl carbamate (TNPC), were compared with those of meprobamate and chloridazepoxide as reference drugs. 1. 1. Oral LD 50 and PD 50 administrations of TNPC were >5000 mg/kg and 1450 mg/kg, respectively. 2. 2. TNPC demonstrated a potent anticonvulsant property against electroshock and chemoshock produced by picrotoxin, strychnine, or pentylenetetrazol. 3. 3. In mice inhibitory actions of TNPC were observed on spontaneous motor activity, fighting episodes, and the stimulating activity and lethality of dl-methamphetamine. Inhibition of the conditioned avoidance response, but not the unconditioned avoidance response, was observed in rats. These effects were observed at levels below the relaxing dose. 4. 4. TNPC exhibited hypothermic action in mice but had no analgesic or sedative action. 5. 5. TNPC had a hypotensive effect in anesthetized cats. This hypotensive effect was not influenced by atropinization, bilateral vagotomy, or removal of bilateral carotid bodies. Also pretreatment with diphenhydramine and dichlorisoproterenol did not influence the hypotensive effect of TNPC. TNPC showed a hypotensive effect in spinal cats, but less strong than that induced in intact animals.

The Effect of Carotid Body Removal on Artificially Induced Bronchospasm Simulating Asthma: An Experimental Study

The left carotid body was removed from 24 guinea pigs and the animals subsequently exposed to 2 per cent histamine aerosol until an “end point” was reached in which breathing changed from rapid thoracoabdominal to slow abdominal type. The times taken for this “end point” to be reached were not found to be significantly different from the times taken in a similar series of control guinea pigs. The experiments suggest that removal of the carotid body does not affect the resistance of the guinea pig to artificially induced bronchospasm.

Responses of aortic chemoreceptors.

ArticleResponses of aortic chemoreceptors.A S Paintal, and R L RileyA S Paintal, and R L RileyPublished Online:01 Mar 1966https://doi.org/10.1152/jappl.1966.21.2.543MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByEffects of carotid and aortic chemoreceptor denervation in newborn pigletsA. Serra, D. Brozoski, M. Hodges, S. Roethle, R. Franciosi, and H. V. Forster1 March 2002 | Journal of Applied Physiology, Vol. 92, No. 3Important role of carotid chemoreceptor afferents in control of breathing of adult and neonatal mammalsRespiration Physiology, Vol. 119, No. 2-3Effect of Independent Changes in Mixed-Venous PCO2or PO2on Cardiac Output in Anesthetized SheepJournal of Surgical Research, Vol. 71, No. 2Role of aortic chemoreceptors in the hypertensive response to cigarette smokeRespiration Physiology, Vol. 106, No. 3Effect of chemoreceptor stimulation on the periodicity of renal sympathetic nerve activity in anesthetized catsJournal of the Autonomic Nervous System, Vol. 37, No. 1Oxygen Sensing by Arterial ChemoreceptorsHow Real Is the Relation of Arterial Po2 to Chemoreceptor Activity?Chapter 18 The responses of chemoreceptors with medullated and non-medullated fibres to chemical substances and the mechanical hypothesisReflex Responses to Chemoreceptor Stimulation1 January 2011Interactions Between Respiration and Circulation1 January 2011Osmosensitive vagal receptors in the small intestine of the catJournal of the Autonomic Nervous System, Vol. 16, No. 3Lung and Airway ReceptorsRole of Peripheral Chemoreceptors and Central Chemosensitivity in the Regulation of Respiration And Circulation1 October 1982 | Journal of Experimental Biology, Vol. 100, No. 1Ventilatory responses to hypocapnic vertebral artery perfusion in intact and carotid body denervated dogsRespiration Physiology, Vol. 45, No. 1Aortic nerve stimulation in the rat: Cardiovascular and respiratory responsesBrain Research Bulletin, Vol. 6, No. 4-6Innervation of the rat aortic (subclavian) body: An ultrastructural study following axonal degenerationJournal of Ultrastructure Research, Vol. 74, No. 1Influence of the depth of anaesthesia on the peripheral and central ventilatory CO2 sensitivity during hyperoxiaRespiration Physiology, Vol. 41, No. 3Restoration of reflex ventilatory response to hypoxia after removal of carotid bodies in the catNeuroscience, Vol. 5, No. 3The failure of differences in neurally contained acetylcholine to explain differences between carotid body and aortic body chemoreceptionBrain Research, Vol. 179, No. 1Carbon dioxide sensitivity of aortic chemoreceptors in the catRespiration Physiology, Vol. 36, No. 3Medullary and carotid chemoreceptor interaction for mild stimuliPfl�gers Archiv European Journal of Physiology, Vol. 374, No. 1Mechanism of increased tracheo-bronchial response to inhalative acetylcholine aerosol in pulmonary vascular congestion and unilateral pulmonary artery occlusionResearch in Experimental Medicine, Vol. 170, No. 3A Functional Estimate of the Local PO2 at Aortic ChemoreceptorsEffects of drugs on chemoreceptors, pulmonary and cardiovascular receptorsPharmacology & Therapeutics. Part B: General and Systematic Pharmacology, Vol. 3, No. 1NATURAL AND PARANATURAL STIMULATION OF SENSORY RECEPTORSStimulus interaction in the responses of carotid body chemoreceptor single afferent fibersRespiration Physiology, Vol. 24, No. 3Relationship between carotid chemoreceptor activity and ventilation in the catRespiration Physiology, Vol. 24, No. 3Cardiovascular ReceptorsA TRIBUTE TO PROFESSOR AUTAR SINGH PAINTAL (1925-2004) More from this issue > Volume 21Issue 2March 1966Pages 543-8 https://doi.org/10.1152/jappl.1966.21.2.543PubMed5934462History Published online 1 March 1966 Published in print 1 March 1966 Metrics

Chemoreflexes in breathing.

Chemoreflexes in breathing.

Resection of carotid body (cervical glomectomy) for asthma.

Intractable asthma which had not been relieved by desensitization, bronchodilators, changes of climate, steroids, and other standard therapeutic methods was treated in 157 patients by removal of one carotid body and in 3 others by removal of both carotid bodies. The glomectomy was done under local anesthesia. Some patients reported noticeable relief either after the novocain was injected into the carotid body, or at the instant of its removal. Slightly over half of the patients were either dramatically or significantly improved. No alterations of blood pressure or of heart rate were observed, and there were no immediate or late untoward sequelae.

Influence of carotid body removal on polycythemia and arterial oxygen saturation during discontinuous anoxia.

ArticleInfluence of Carotid Body Removal on Polycythemia and Arterial Oxygen Saturation During Discontinuous AnoxiaWilson C. GrantWilson C. GrantFrom the Department of Physiology, College of Physicians and Surgeons Columbia University, New York CityPublished Online:31 Dec 1950https://doi.org/10.1152/ajplegacy.1950.164.1.226MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation More from this issue > Volume 164Issue 1December 1950Pages 226-233 Copyright & PermissionsCopyright © 1950 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1950.164.1.226History Received 22 June 1950 Published online 31 December 1950 Published in print 31 December 1950 Metrics