Chemoreceptor Tissue Research Articles

Effect of arterial chemoreceptor stimulation: role of norepinephrine in hypoxic chemotransmission.

Mammalian carotid bodies contain substantial amounts of norepinephrine (NE) (1,2). Despite its abundance in the chemoreceptor tissue, the role of norepinephrine in carotid body function remain uncertain. Several investigators have examined the effects of norepinephrine on carotid body activity (3–6). The reported chemoreceptor responses to NE include inhibition as well as excitation, often inhibition preceeds the excitation.

Aortic and carotid body chemoreception in prolonged hyperoxia in the cat

Carotid body chemisensory response to hypoxia is attenuated as a result of prolonged normobaric hyperoxia (NH) in the cat. The effect of NH is likely to be due to high cellular P o2 and O 2-related free radicals. Accordingly, the effect would be less if O 2 delivery to the chemoreceptor tissue could be compromised. The aortic bodies, which appear to have less of a circulatory O 2 delivery, as suggested by their vigorous responses to a slight compromise of O 2 flow compared with those of the carotid body, could provide a suitable testing material for the hypothesis. We tested the hypothesis by studying both aortic and carotid body chemoreceptors in the same cats ( n=6) which were exposed to nearly 100% O 2 for about 60 h. These chemoreceptor organs were also studied in 6 control cats which were maintained in room air at sea-level. The cats were anesthetized and their carotid and aortic chemosensory fibers were identified by the usual procedure, and their responses to hypoxia and hypercapnia and to bolus injections (i.v.) of cyanide and nicotine were measured. In the NH cats, the carotid but not aortic chemosensory responses to hypoxia and cyanide were attenuated and to hypercapnia (both onset and steady state) augmented. The aortic chemoreceptors were stimulated by hypoxia, hypercapnia, cyanide and nicotine both in the NH and the control cats similarly. The results support the hypothesis that is presumably a higher tissue blood flow and hence a higher concentration of O 2-related free radicals which ultimately led to the specific attenuation of O 2 chemoreception in the carotid body.

The role of cyclic AMP in chemoreception in the rabbit caroid body

The present study identified physiological factors which influence the generation (and degradation) of cyclic AMP (cAMP) in the arterial chemoreceptor tissue of the mammalian carotid body. Experiments established a 3-way correlation between cAMP generation, neurotransmitter release from chemoreceptor cells, and carotid sinus nerve (CNS) activity. Incubation of carotid bodies in vitro for 10 min in media equilibrated with different low O 2 (‘hypoxic’) gas mixtures (5% O 2 or 10% O 2, balance N 2) elevated basal cAMP levels (100% O 2 media) in proportion to the stimulus intesity. Similar experiments using nodose sensory ganglia showed that low O 2 stimulation did not alter cAMP levels in this non-chemosensory tissue. However, the adenylate cyclase (AC) activator, forskolin (10 μM), evoked large increases in the cyclic nucleotide content in both carotid bodies and nodose ganglia. After chronic (10 days) CSN denervation or synpathectomy, the basal levels of cAMP in the carotid body were elevated; the cAMP response to low O 2 media (stimulus minus control) was increased after CSN denervation but remained unaltered after sympathectomy. The effects of zero Ca 2+ media on cAMP generation was examined in order to assess whether feedback from released neurotransmitters acting on known (presynaptic) type I cell receptors could have contributed to the observed changes in cAMP. Basal levels of cAMP were increased 2.8-fold, and the response to hypoxic stimulation was elevated 5-fold, in the absence of extracellular Ca 2+. Forskolin (10 μM) did not alter basal release of [ 3H]-catecholamines ([ 3H]CA: synthesized from [ 3H]tyrosine, or resting CSN discharge; however, stimulus-evoked [ 3H]CA release and CSN discharge were potentiated in the presence of forskolin. This increased release was primarily due to enhanced efflux of dopamine (DA). At increasing stimulus strengths, however, the relative effect of forskolin on [ 3H]CA release was diminished. The data suggest that the chemoreceptor type I cells in the carotid body generate cAMP in their transductive response to hypoxia, but that the net levels of cAMP in the tissue are also regulated by both feedback actions of released neurotransmitters and by the sympathetic and sensory innervation to the organ. The effects of forskolin on [ 3H]CA release and CSN activity, combined with the finding that hypoxia increases the cAMP content of the carotid body, suggest the immediate invlovement of this classical second messenger in chemotransduction and chemotransmission of natural carotid body stimuli.

Differential stimulus coupling to dopamine and norepinephrine stores in rabbit carotid body type I cells

Recent studies suggest that preneural type I (glomus) cells in the arterial chemoreceptor tissue of the carotid body act as primary transducer elements which respond to natural stimuli (low O 2, pH or increased CO 2) by releasing chemical transmitter agents capable of exciting the closely apposed afferent nerve terminals. These type I cells contain multiple putative transmitters, but the identity of the natural excitatory agents remains an unresolved problem in carotid body physiology. Characterization of putative transmitter involvement in the response to natural and pharmacological stimuli has therefore become fundamental to further understanding of chemotransmission in this organ. The present study demonstrates that a natural stimulus (hypoxia) evokes the release of dopamine (DA) and norepinephrine (NE) in approximate proportion to their unequal stores in rabbit carotid body (DA release/NE release = 8.2). In contrast, nicotine (100 μM), a cholinomimetic agent thought to act on the nicotinic receptors present on the type I cells, evokes the peferential release of NE (DA release/NE release = 0.17). These findings suggest that distinct mechanisms are involved in a differential mobilization of these two catecholamines from the rabbit carotid body.

Carotid and aortic bodies in chronically anemic normotensive and spontaneously hypertensive rats

Overactivity of the carotid body chemoreceptors along with the enlargement of chemoreceptor tissue were found in spontaneously hypertensive rats of Okamoto-Aoki strain (SHR). The purpose of the present study was to answer the question whether the aortic bodies were also enlarged in SHR. However, because aortic bodies, unlike carotid ones, are sensitive to oxygen content another question arose: do aortic bodies undergo hypertrophy in chronic anemia? Twenty-three spontaneously hypertensive rats of Okamoto-Aoki strain (SHR) and 24 normotensive Wistar rats (NCR) were maintained on low-iron food from the age of 3 weeks. In seven 10-week-old anemic SHR regular diet was substituted (transiently anemic SHR). Blood pressure measurements and hemoglobin were measured every second week. The animals were killed at the age of 18 weeks. Light microscopic studies of the carotid and aortic bodies were performed and volumes of chemoreceptor tissues were determined from serial sections. The eight SHR on low-iron diet exhibited lower hemoglobin concentration than their normotensive counterparts. In the anemic SHR blood pressure was lower than in control SHR, whereas blood pressure did not differ between the anemic and control NCR. Restoration of normal values of hemoglobin in the anemic SHR was followed by only a slight increase in blood pressure. The carotid bodies volumes were 2.5–3 times larger in the SHR than in NCR. The volumes of carotid bodies both of the SHR and NCR were influenced neither by blood pressure nor by hemoglobin concentration. The aortic bodies were more numerous in SHR than in NCR. Enlargement of aortic bodies found in the anemic SHR was not visible in the transiently anemic SHR. The aortic bodies of NCR were not affected by decreased hemoglobin concentration. Less severe anemia not followed by any changes in blood pressure in the NCR is a plausible explanation of the lack of enlargement of aortic bodies in these rats.

Peptidergic innervation of arterial chemoreceptors.

The peptidergic innervation of arterial chemoreceptor organs (the rat carotid body and vagal paraganglia; guinea pig carotid body) was studied immunohistochemically. Five different populations of nerve fibres in the guinea pig carotid body could be discriminated according to their origin and their chemical coding. The innervation pattern of the rat carotid body differed in some aspects. Comparison of the rat carotid body and vagal paraganglia suggested that autonomic neuropeptide Y-like immunoreactive fibres act primarily via vascular mechanisms rather than directly on the chemoreceptor tissue. Sensory fibres were shown to contain immunoreactivities for substance P, calcitonin gene-related peptide (rat and guinea pig) and somatostatin (guinea pig). The functional role of the identified peptide-containing sensory fibres remains to be established.

Do arterial chemoreceptors play a role in the pathogenesis of hypertension?

Although the arterial chemoreflex exerts a powerful influence upon the cardiovascular system, this reflex has until now been a disregarded factor in hypertension research. By comparing the physiological effects of chemoreceptor excitation to disarrangements present during the early labile phase of hypertension in spontaneously hypertensive rats, we found remarkable similarities. A search through the literature as well as our experimental data fully confirm this association. Many factors, among them decreased blood flow through the glomic tissue, lead to chemoreceptor stimulation. The origins of the chemoreceptor arteries are located in areas very susceptible to atherosclerotic changes which can lead to ischemia of chemoreceptor tissue. We are led to hypothesize that arterial chemoreflex is a significant factor in the etiology of essential hypertension.

Anatomic and physiologic considerations of a cardiogenic hypertensive chemoreflex

Within both human and canine hearts there is a mass of chemoreceptor tissue lying just between the origins of the aorta and pulmonary artery and receiving its blood supply from the proximal portion of the left coronary artery. In the dog this is considered to be the site of origin for a powerful hypertensive reflex stimulated by serotonin. There is brief generalized arterial vasoconstriction, except for the coronary and pulmonary arteries. The afferent limb of this cardiogenic hypertensive Chemoreflex courses in thoracic branches of the vagus. Autonomic efferent responses are both vagal arid, sympathetic events. These include simultaneous positive and negative inotropic effects on the atria, a positive inotropic effect on both ventricles, positive and negative chronotropic actions and similarly mixed dromotropic effects. Methods for separately identifying and quantifying these responses are discussed and illustrated. Vagotomy eliminates the reflex, as does the administration of cyproheptadine (but not methysergide). Among possible human counterparts for this cardiogenic hypertensive Chemoreflex are the pressor responses associated with angina pectoris, with very early acute myocardial infarction and after certain forms of cardiac surgery such as saphenous vein bypass grafting.

Chemodectomas of the Carotid Body and Glomus Tympanicum

CHEMODECTOMA of the carotid body is uncommon; fewer than 550 cases have been reported. A familial tendency toward development of chemodectomas in the contralateral carotid body or in other sites where chemoreceptor tissue is found has been documented. This familial occurrence and the tendency of chemodectomas of the carotid body to be bilateral or multiple when patients have relatives with chemodectomas deserve emphasis. We have treated two sisters for tumors of the glomus tympanicum who returned several years later with carotid body tumors. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 47-year-old woman noted a sense of fullness in her left ear in 1960. She was examined in South Carolina, and a tumor of the glomus tympanicum was located and excised. She underwent three subsequent excisions and was seen by one of us (M.L.L.) in 1969; an excision of a recurrent tumor of the glomus tympanicum was performed. Six months later she

Chemodectomas of the carotid body and glomus tympanicum. Sequential occurrence in sisters

CHEMODECTOMA of the carotid body is uncommon; fewer than 550 cases have been reported. A familial tendency toward development of chemodectomas in the contralateral carotid body or in other sites where chemoreceptor tissue is found has been documented. This familial occurrence and the tendency of chemodectomas of the carotid body to be bilateral or multiple when patients have relatives with chemodectomas deserve emphasis. We have treated two sisters for tumors of the glomus tympanicum who returned several years later with carotid body tumors. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 47-year-old woman noted a sense of fullness in her left ear in 1960. She was examined in South Carolina, and a tumor of the glomus tympanicum was located and excised. She underwent three subsequent excisions and was seen by one of us (M.L.L.) in 1969; an excision of a recurrent tumor of the glomus tympanicum was performed. Six months later she

High altitude hypoxia and chemodectomas

Twenty-three of 25 Peruvian adults with chemodectomas of the head and neck had been born and lived at altitudes between 2105 and 4350 meters (6904 to 14,268 feet). Estimates of prevalence in Peru indicate that chemodectomas are about 10 times more frequent at high altitudes than at sea level. All carotid body tumors in the high altitude patients were benign; one other patient had a malignant glomus jugulare tumor. Females predominated over males in the proportion of 6.33:1 and left sided carotid body tumors over right sided in a ratio of 3.20:1. In only one instance was the carotid body tumor bilateral. One-half of the high altitude patients with carotid body tumors also had significant respiratory abnormalities. The present observations suggest that carotid body tumors in the high altitude native represent the extreme degree of hyperplastic response of chemoreceptor tissue to prolonged and severe hypoxia.

Pulmonary venous chemoreceptor tissue

Histological examination of a block of lung from necropsy on a woman of 67 years who died from a pontine haemorrhage revealed a nodule of chemoreceptor tissue deep in the lung around small pulmonary veins. Such nodules have been regarded as minute chemodectomas but may in fact represent hyperplasia of chemoreceptor cells normally present around small pulmonary veins.

Pulmonary venous chemoreceptor tissue

Histological examination of a block of lung from necropsy on a woman of 67 years who died from a pontine haemorrhage revealed a nodule of chemoreceptor tissue deep in the lung around small pulmonary veins. Such nodules have been regarded as minute chemodectomas but may in fact represent hyperplasia of chemoreceptor cells normally present around small pulmonary veins.

Hypoxic ventilatory drive in normal man.

A technique is described which permits the inscription of the ventilatory response to isocapnic hypoxia in man as a continuous curve relating alveolar oxygen tension and minute ventilation. The adjustment of ventilation to changes in alveolar oxygen tension is complete in 18-23 sec and this is sufficiently rapid to justify the use of a non-steady-state method. Changes in alveolar carbon dioxide tension are prevented by addition of carbon dioxide to the inspired gas. The resulting [unk]V(E)-P(Ao2) curves are hyperbolic such that falling P(Ao2) produces only slight rises in [unk]V(E) until a critical P(Ao2) range of 50-60 mm Hg is reached. With further fall in P(Ao2), [unk]V(E) increases steeply and the slope of the curve approaches infinity at a tension of 30-40 mm Hg. For purposes of quantitation these curves are approximated by a simple hyperbolic function, the parameters of which are evaluated by a least squares fit of the data. The parameter A denotes curve shape such that the higher the value of A. the greater the increase in ventilation for a given decrease in P(Ao2) and hence the greater the hypoxic drive. Curves are highly reproducible for each subject and curves from different subjects are similar. In 10 normal subjects at resting P(ACo2), A = 180.2 +/-14.5 (SEM). When P(ACo2) is adjusted to levels 5 mm Hg above and below control in six subjects A = 453.4 +/-103 and 30.2 +/-6.8 respectively. These latter values differed significantly from control (P < 0.05). These changes in curve shape provide a clear graphic description of interaction between hypercapnic and hypoxic ventilatory stimuli. At normal P(ACo2) the [unk]V(E)-P(Ao2) curve has an inflection zone located over the same P(o2) range as the inflection in the oxygen-hemoglobin dissociation curve. This indicated that ventilation might be a linear function of arterial oxygen saturation or content. Studies in four subjects have demonstrated that ventilation is indeed related to arterial oxygen content in a linear fashion. These data suggest, but do not prove, that oxygen tension in chemoreceptor tissue as in part determined by circulatory oxygen delivery may be an important factor in controlling the ventilatory response to hypoxia.

Decreased ventilatory response to hypoxia during acute polycythemia in the calf

Increase in ventilation in response to acute hypoxia is mediated by stimulation of systemic arterial chemoreceptors. Probably the stimulus is intracellular hypoxia resulting from a reduction m the amount of oxygen delivered to the chemoreceptor tissue. If oxygen transport were increased, then the ventilatory response to hypoxia might be reduced. This hypothesis was examined in nine calves. Blood oxygen carrying capacity was increased by the infusion of packed red cells sufficient to increase the hemoglobin concentration from 11.4 to 15.7 g/100 ml, which increased systemic oxygen transport by 37%. Lowering the arterial oxygen tension from 60 to 40 mm Hg increased ventilation 141% prior to transfusion, but only 76% in the presence of polycythemia (p < .005). However, polycythemia did not alter significantly the ventilatory response to hypereapnia in the absence of hypoxia. It is postulated that in the presence of a given degree of arterial hypoxemia, polycythemia augments oxygen transport to lessen chemoreceptor tissue hypoxia and thereby reduce the stimulation of ventilation.

Chemodectoma of the orbit.

The histological and clinical features of a primary chemodectoma arising in the orbit are described. It is suggested that the tumour may have arisen from chemoreceptor tissue in the area of the lacrimal gland.

Surgical management of cervical paragangliomata.

Since Marchand first described a new growth arising from the carotid body in 1891, over 600 carotid body tumors and 300 glomus jugulare neoplasms have been reported in the literature.1-3Despite their relative infrequency, these lesions have created considerable controversy over pathologic classification, biologic behavior, diagnosis, and treatment. Two recent cases of atypically located carotid body tumors presenting as posterior pharyngeal masses, and recent evidence that suggests that a proper classification of tumors of chemoreceptor tissue awaits additional knowledge of tumor hormone metabolism, has prompted a review of the current concepts of the behavior, diagnosis, and management of cervical paragangliomata.4Twenty-one patients with cervical chemodectomas have been treated at the University of Kansas Medical Center since 1958, and form the basis of this report. Anatomy and Embryology The carotid body is an ovoid structure located near the carotid bifurcation that contains the largest collection of chemoreceptor tissue in

The aorticopulmonary artery of the cat--its location and postnatal closure.

AbstractThis paper describes the position and time of postnatal closure of a vessel from the pulmonary artery to the aorticopulmonary glomus (carotid body‐like) tissue. Nine prenatal and eight postnatal kittens (killed at 12 hours, and 8, 12, 16, 30, 42, 60 and 90 days) and 50 adult cats were examined. The vessel arose from the root of the right pulmonary artery and had ascending and descending branches. The latter supplied the aorticopulmonary glomus tissue and mingled with vessels arising from the root of the coronary arteries — usually the left. In two prenatal cats an actual anastomosis was demonstrated. There was no change in the intramural part of the branch of the pulmonary artery in kittens less than 16 days old. The vessel was partly closed by cellular proliferation by the sixteenth day and was almost certainly occluded by the forty‐second day. It was not patent in any animal more than 42 days of age. In the adult cat, the aorticopulmonary glomus tissue was less cellular than in the fetus. It is suggested that the communication between the branch from the right pulmonary artery and the coronary arteries through chemoreceptor tissue may have functional significance.

A clinical method for assessing the ventilatory response to carbon dioxide.

SummaryA simple method of studying the regulation of ventilation has been developed so that rapid serial observations can be made in sick patients. The method is based on the progressive increase of Pco2 and the resulting stimulation of ventilation which occurs during rebreathing from a bag. A small bag is used in which the initial Pco2 is close to the Pco2 of mixed venous blood. With this technique, a Pco2 equilibrium is rapidly established between mixed venous blood, arterial blood and end‐expiratory gas. Subsequently, parallel changes develop in end‐expiratory Pco2 and ventilation. Under these conditions, changes in end‐expiratory Pco2 reflect the changes of medullary chemoreceptor Pco2 and the developing carbon dioxide stimulus.Experiments are reported which establish the linearity, reproducibility and normal range of response‐curves relating ventilation (V̇E) to end‐expiratory Pco2. These V̇E/Pco2 response‐lines were only slightly disturbed by simulated abnormality of the body carbon dioxide storage capacity or acute depletion of the body carbon dioxide stores. V̇E/Pco2 response‐lines obtained by rebreathing and by the prolonged steady‐state method differed significantly in position but not in slope. The similarity in slope implies that the same proportion, Δ end‐expiratory Pco2/Δ chemoreceptor Pco2, is established for the two methods. The difference in position indicates a smaller Pco2 gradient between arterial blood and chemoreceptor tissue in the rebreathing method.The method is particularly suited for clinical use, being rapid, tolerable and easily repeated. It avoids the necessity for sampling arterial or internal jugular venous blood, and can be performed by the bedside with the use of simple apparatus.

Two unusual tumours of the chemoreceptor system with angiographic demonstration.

Two cases of tumours of chemoreceptor tissue with angiographic demonstration have been reported. The first case was unusual as it was a tumour of the glomus intravagale and was extensively calcified. The second case with three chemodectomas (glomus jugulare, carotid body and glomus intravagale) illustrates the uncommon multicentric manifestation of these neoplasms.