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At least 19 recordsLinked to original sources

Role of substance P in neutral endopeptidase modulation of hypoxic response of the carotid body.

Carotid body expresses neutral endopeptidase (NEP)-like enzyme activity and phosphoramidon, an inhibitor of NEP augments sensory response of the carotid body to hypoxia (Kumar et al., 1990). NEP hydrolyzes substance P (SP) and methionine enkephalin (Met-ENK) in the nervous system. In the present study, we determined whether NEP hydrolyzes Met-ENK and SP in the carotid body and whether these peptides contribute to the phosphoramidon-induced potentiation of the sensory response to hypoxia. Experiments were performed on carotid bodies excised from anaesthetized adult cats. HPLC analysis showed that both SP and Met-ENK were hydrolyzed by the carotid body. Phosphoramidon (400 microM) markedly inhibited SP (approximately 90%) but had only marginal effect on Met-ENK hydrolysis (approximately 15%). Sensory responses of the carotid body in vitro to hypoxia (pO2, 68 +/- 6 mmHg) and SP (10 nmoles) were potentiated by phosphoramidon by approximately 80% and approximately 275% respectively (p < 0.01). SP-receptor antagonist abolished phosphoramidon-induced potentiation of the sensory response to hypoxia as well as to SP. These results demonstrate that SP is a preferred substrate for NEP in the carotid body and SP plays a major role in the potentiation of the hypoxic response of the carotid body by phosphoramidon.

Animals↗

The paraganglia within the carotid bifurcation regions of young and old spontaneously hypertensive rats (SHR) after exposure to chronic hypobaric hypoxia. I. The carotid bodies.

Carotid body volumes and the histological appearance of these chemoreceptors were studied using light microscopic methods in 10 groups of spontaneously hypertensive rats (SHR). The aim of this study was to clarify the influence of chronic hypobaric hypoxia on the carotid bodies of SHR depending on the age of the rats, on the duration of exposure to hypoxia, and on different salt intake, respectively different blood pressure. We found that: 1. The carotid bodies of chronically hypoxic SHR are enlarged. 2. The degree of carotid body enlargement is dependent on the duration of exposure to hypoxia. 3. In old SHR the increase of carotid body volume was smaller than in young SHR. 4. Old chronically hypoxic SHR exhibited more distinct vascular changes in the carotid bodies than age-matched normoxic controls as well as younger chronically hypoxic and normoxic SHR. 5. The influence of different levels of systemic arterial blood pressure on the carotid body volumes was rather small compared with the effects of chronic hypobaric hypoxia.

Age Factors↗

Ultrastructure of calcitonin gene-related peptide- and substance P-like immunoreactive nerve fibres in the carotid body and carotid sinus of the guinea pig.

Previous studies have demonstrated that substance P- (SP) and calcitonin gene-related peptide-like immunoreactivities (CGRP-LI) coexist in sensory nerve fibres in the guinea-pig carotid body and carotid sinus. In the present study the ultrastructure of these nerve fibres was investigated by means of single- and double-labelling immunocytochemistry. In both, carotid body and carotid sinus immunoreactive fibres were unmyelinated axons of small diameter (0.12-0.56 microns). At the subcellular level, SP- and CGRP-LI were colocalized in intra-axonal dense core vesicles, suggesting corelease and simultaneous action of these two compounds. SP/CGRP-LI nerve fibres within the carotid body were mainly found in the interparenchymal connective tissue, but also occurred in relationship to blood vessels and nests of glomus cells. Neither in the carotid body not in the carotid sinus, SP/CGRP-LI axons corresponded to the large terminals which are generally considered to represent the main chemoreceptor and baroreceptor endings, respectively. Thus, SP/CGRP-LI fibres either belong to the chemo- and baroreceptors of the C-fibre class or constitute a fibre population not directly involved in conduction of baro- and chemoreflexes.

Animals↗

Effects of chronic hypoxia on opioid peptide and catecholamine levels and on the release of dopamine in the rabbit carotid body.

Carotid body catecholamine and opioid levels were measured in rabbits exposed for 8 days to an atmosphere of 11% O2 in N2 (PO2 of approximately 80 mm Hg) and during an identical period of recovery, i.e., after 8 days of returning to the control normoxic atmosphere. Carotid bodies show a decrease in dopamine content at day 2. Thereafter, the levels of this biogenic amine increase progressively to peak at day 10, that is, 2 days after returning to a normoxic atmosphere. Finally, dopamine levels start to decrease and reach prehypoxic control levels at day 16, that is, after 8 days of recovery. In contrast, levels of native opioid peptides remain unchanged during the whole duration of the experiment, except for a decrease at day 2 of the hypoxic exposure. Levels of total opioid peptides are also below control values at day 2 of hypoxia, increase above control values on returning to a normoxic atmosphere (maximal levels at days 10-12), and later decrease to reach prehypoxic levels at day 16. As a result of these changes the ratios of dopamine to opioid levels show a progressive increase from day 0 to day 10 of the experiment and then return to control prehypoxic values. Carotid bodies isolated from animals that have been exposed to hypoxia for 8 days synthesize [3H]dopamine from its natural precursor [3H]tyrosine at a rate of 175 pmol/mg of protein/h, which is about double the rate of synthesis found in the carotid bodies of control animals and those allowed to recover for 8 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of glucocorticoid treatment on catecholamine content and ultrastructure of adult rat carotid body.

Carotid bodies of dexamethasone-treated (daily injections, 10 days) adult male rats were analyzed with respect to catecholamine content and ultrastructure. Gas chromatographic-mass spectrometric assays demonstrated that norepinephrine (NE) and dopamine (DA) concentrations more than doubled after dexamethasone treatment. The increase in NE was relatively greater than that of DA. No epinephrine (E) could be detected. Morphometry revealed, as for the control carotid bodies, two subclasses of type I cells on the basis of the diameters of their dense-cored vesicles. These groups of cells were termed small vesicle cells (SVC) and large vesicle cells (LVC). Dexamethasone treatment resulted in significantly increased volume densities and diameters of the dense-cored vesicles in both SVC and LVC. The greatest increase occurred in the SVC. If these morphological changes do reflect the change in amine concentrations then it is possible to speculate that the type of cells with the greatest increase of amine storage capacity may store the kind of catecholamine most increased. Thus NE may presumably be stored in the SVC and DA in the LVC. Furthermore, these effects of administered glucocorticoids may also indicate a regulatory function for endogenous glucocorticoids on the carotid body catecholamines.

Animals↗

In vitro recording of chemoreceptor activity in catecholamine-depleted rabbit carotid bodies.

Carotid bodies, together with Hering's nerves, were excised from anesthetized rabbits 24, 48 or 72 h after single reserpine injections (5 mg kg-1, i.v. or i.p.) and were superfused in vitro. Some carotid bodies were processed for formaldehyde-induced fluorescence microscopy to assess catecholamine depletion. Twenty-four hours after reserpine treatment, most of the type I cell islets had lost their fluorescence and the number of spontaneously active chemoafferent units was dramatically reduced. Forty-eight hours after reserpine injection, both the fluorescence of type I cells had partially recovered and the number of chemoreceptor units was almost normal. A significant reduction of both the normoxic and hypoxic frequencies of discharge was demonstrated in carotid bodies examined 24 or 48 h after reserpine pretreatment. Superfusions with dopamine (1, 10, 100 microM) transiently restored the response to hypoxia. It is proposed that catecholamines contained in type I cells play a prominent role in the genesis of chemoafferent activity and in the chemoreceptor response to hypoxia.

Animals↗

Nitric oxide synthase in the rat carotid body and carotid sinus.

The participation of nitric oxide synthase (NOS) in the innervation of the rat carotid body and carotid sinus was investigated by means of NADPH-diaphorase histochemistry and NOS immunohistochemistry using antisera raised against purified neuronal NOS and a synthetic tridecapeptide. NOS was detected in 23% of neurons at the periphery of the carotid bodies. Some negative neurons were surrounded by NOS-positive terminals. NOS-containing varicose nerve fibres innervated the arterial vascular bed and, to a lesser extent, the islands of glomus cells. These fibres persisted after transection of the carotid sinus nerve and are probably derived from intrinsic neurons. Large NOS-positive axonal swellings in the wall of the carotid sinus were absent after transection of the sinus nerve, indicating their sensory origin. The results suggest a neuronal nitrergic control of blood flow, neuronal activity and chemoreception in the carotid body, and an intrinsic role of NO in the process of arterial baroreception.

Amino Acid Oxidoreductases↗

The presence of CO2/HCO3- is essential for hypoxic chemotransduction in the in vivo perfused carotid body.

Carotid chemoreceptor activity was increased by the perfusion of the carotid body in vivo with hypoxic HEPES-buffered solution (HBS) containing CO2/HCO3- (HBA+), but not with hypoxic HBS without CO2/HCO3- (HBS-). When the perfusate was switched to hypoxic HBS+ during hypoxic HBS-perfusions, chemoreceptor activity increased immediately. Thus, CO2/HCO3- played a critical role in the hypoxic chemotransduction of the in vivo perfused carotid body.

Animals↗

The relation between carotid body chemoreceptor discharge, carotid sinus pressure and carotid body venous flow.

1. Activity in forty-two single chemoreceptor afferent fibres from the carotid body in thirty-nine cats was measured when the carotid body was naturally and artificially perfused. In nine of these cats, carotid body venous flow was also measured.2. When pressure within the carotid sinus segment was suddenly raised or lowered, chemoreceptor activity changed in the opposite direction within the first 5-10 sec by an amount which was significantly greater than the variation of activity in the control period. Thereafter activity stabilized at a level which was not different from control.3. Whether the carotid body was naturally or artificially perfused, carotid body chemoreceptor activity, following this initial transient change, was unaffected in eight out of twelve fibres by alterations in carotid sinus pressure within the range 60-160 mm Hg and carotid body venous flow 10-60 mul./min, blood gas tensions and pH being maintained constant. In the four remaining fibres, chemoreceptor activity increased slightly but significantly as pressure was lowered in this range. Chemoreceptor activity increased in all fibres tested when pressure was lowered below 50-60 mm Hg.4. Chemoreceptor response curves to changes in P(a,O2) (30-450 mm Hg), P(a,CO2) (27-62 mm Hg) or [H(+)](a) (3-7 x 10(-5) m-equiv/l.) were not significantly different whether the carotid body was perfused (a) naturally at the prevalent systemic pressure, (b) artificially at the same pressure, or (c) artificially at one higher pressure, 130 or 140 mm Hg.5. These results indicate that the carotid body chemoreceptors are relatively unaffected by sustained changes in arterial pressure or in total carotid body flow within the physiological range.

Animals↗

Characterization and developmental changes of Na+ currents of petrosal neurons with projections to the carotid body.

Carotid body chemoreceptors transduce a decrease in arterial oxygen tension into an increase in spiking activity on the sinus nerve, and this response increases with postnatal age over the first week or two of life. Previous work from our laboratory has suggested a major role of axonal Na(+) channels in the initiation of afferent spiking activity. Using RT-PCR of the petrosal ganglia we identified Na(+) channel TTX-S isoforms Na(v)1.1, Na(v)1.6, and Na(v)1.7 and the TTX-resistant (TTX-R) isoforms Na(v)1.8 and Na(v)1.9 at high levels. Electrophysiologic recordings (at 3 ages: 3 days, 9 days, 18-20 days) of neurons that project to the carotid body exhibited predominantly fast-inactivating sodium currents, with a bimodal recovery from inactivation at -80 mV (fast component approximately 8 ms; slow component approximately 90 ms). Developmental age had little effect with no change in peak current density (approximately 1.4 nA/pF) and was associated with a slight, but significant increase in the speed of recovery from inactivation at -140 and -120 mV but not at other potentials. Assuming that the same Na(+) channel complement is present at the nerve terminal as at the soma, the association of a sensory modality (chemoreception) with a relatively uniform Na(+) channel profile suggests that the rapid kinetics of TTX-S channels may be essential for some aspects of chemoreceptor function beyond mediating simple axonal conduction.

Animals↗

[Morphology and topography of the carotid body and carotid sinus in sheep (Ovis ammon f. aries L., 1758)].

The studies were conducted on 60 preparations of 30 sheep heads. The objective of the work was to describe the form, structure, situation, innervation and blood supply of the carotid body and carotid sinus in the sheep. It results from the present study that the carotid body of the sheep is a single formation, of an oval, circular or irregular shape. In most cases it lies on the surface of the medial termination of the common carotid artery and is situated closer to or farther from one of the arteries which begin in this region. The size of the body varies between 1.4 and 2.6 mm in diameter. The initial part of the occipital artery and the posteriorly adjacent dorso-lateral and medial part of the common carotid artery were recognized as the homologue of the carotid sinus of other animals. The carotid body is innervated by the carotid sinus branch of the glossopharyngeal nerve and by the branches of the external carotid nerves. The carotid sinus is innervated by the nerves described above, by a branch of the vagus nerve (in 50% of cases) and by a branch of the hypoglossal nerve (in 23.3% of cases).

Animals↗

Postnatal maturation of neuroepithelial bodies and carotid body innervation: a quantitative investigation in the rabbit.

The intrapulmonary airways contain oxygen-sensitive chemoreceptors which may be analogous to the arterial chemoreceptors: the neuroepithelial bodies (NEB). While the NEB are prominent in the neonatal lung, physiological studies indicate that the carotid bodies are still relatively inactive at birth. This points to an unequal degree of development of both during the early neonatal period. As a reflexogenic chemoreceptor function depends on a well-developed innervation, we undertook a comparative investigation of the development of the NEB and the carotid body glomus cell innervation. Two morphological aspects of the innervation of NEB and carotid body glomus cells were quantified in rabbits of different age groups. The total sectional area of intracorpuscular and intraglomerular nerve endings per NEB or glomus cell group, respectively, was measured and the area percentage of mitochondria and synaptic vesicles was determined. In the NEB, no significant difference in total sectional area of the nerve endings between the age groups was observed, while in the carotid body there was a significant increase in the adult age group. In addition, the area percentage of mitochondria and synaptic vesicles of the nerve endings did not change significantly with age in the NEB, while in the carotid body these increased and decreased, respectively, with age. These observations point to a shift from morphologically efferent nerve endings, rich in synaptic vesicles, to morphologically afferent nerve endings, rich in mitochondria. Our interpretation of these findings is that, at birth, the NEB innervation is more mature than the carotid body glomus cell innervation and that the latter matures at a later time than the former. These findings support the theory that the NEB may act as complementary chemoreceptors to the carotid body during the early postnatal period.

Age Factors↗

Relative responses of aortic body and carotid body chemoreceptors to carboxyhemoglobinemia.

The effects of carbon monoxide inhalation and of consequent carboxyhemoglobinemia (HbCO) on the discharge rates of aortic body and carotid body chemoreceptor afferents were investigated in 18 anesthetized cats. In 10 experiments both aortic and carotid chemoreceptor activities were monitored simultaneously. Carbon monoxide inhalation during normoxia always stimulated aortic chemoreceptors before carotid chemoreceptors, and the steady-state response of aortic chemoreceptors to HbCO was greater than that of most carotid chemoreceptors. Only 2 of the 18 carotid chemoreceptor fibers tested showed a distinct increase in activity in response to moderate increases in HbCO%. Thus, oxyhemoglobin contributed substantially to maintain tissue PO2 of all aortic chemoreceptors and of a few carotid chemoreceptors. Hyperoxia diminished the response of both aortic and carotid chemoreceptors to HbCO, indicating a lowered tissue PO2 as the stimulus source. We hypothesize that the aortic bodies have a much lower perfusion relative to their O2 utilization compared to the carotid bodies. As a consequence, the aortic chemoreceptors are able to act as a sensitive monitor of O2 delivery and to generate a circulatory chemoreflex for O2 homeostasis. carotid chemoreceptors monitor O2 tension and initiate strong reflex effects on the level of ventilation.

Animals↗

The hemodynamic effects of local anesthetic injection into the carotid body during carotid endarterectomy.

Hemodynamic changes consisting of hypertension, hypotension, or bradycardia are commonly seen in patients undergoing carotid endarterectomy. It is a potentially serious clinical problem that may increase mortality rates or incidence of neurologic deficits. The frequency of hemodynamic alterations has been believed to be related to the proximity of the carotid sinus baroreceptor to the endarterectomized region. Consequently, intraoperative or postoperative injection of local anesthetics into the carotid body have been recommended to help offset this compensatory mechanism. However, its effectiveness has not been thoroughly studied. We examined this situation with a prospective, randomized, double-blind clinical study consisting of 99 patients. Xylocaine (short-acting anesthetic), bupivacaine (long-acting anesthetic), or saline (control) was injected into the carotid body intraoperatively. Intraoperative and postoperative hemodynamic changes were then closely monitored and evaluated. We were unable to detect a significant difference in hypotension, hypertension, or bradycardia either during or after surgery. Therefore, on the basis of this study, routine use of local anesthetic injection into the carotid body cannot be recommended.

Aged↗

Relative responses of aortic body and carotid body chemoreceptors to hypotension.

Responses to acute arterial blood pressure changes of a single or a few chemoreceptor afferents from the aortic body and carotid body at constant arterial blood gases and pH were measured in 16 adult cats. During normocapnic normoxia and moderate hypoxia (arterial oxygen tension of 60 Torr) an induced hypotension of 80 Torr increased strikingly the discharge rate of all aortic chemoreceptors but not of most carotid chemoreceptors; hypotension down to the level of 50 Torr stimulated most carotid chemoreceptors only slightly. Hyperoxia eliminated the stimulatory effect of this degree of hypotension on carotid chemoreceptors; it did not affect aortic chemoreceptors to the same extent. Hypoxia augmented the effect on aortic chemoreceptors more than the effect on carotid chemoreceptors. Thus the effect of hypotension was dependent on arterial oxygen tension. The greater effect of hypotension on aortic body chemoreceptor activity indicates a greater normal circulatory constraint for the aortic body. Accordingly, aortic chemoreceptors are more suited to monitor circulatory changes in O2 flow, and carotid chemoreceptors are more suited to monitor arterial gas pressure changes due to respiration.

Animals↗