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PubMed1983

Effect of chemoreceptor and pulmonary receptor stimulation on dilator nares EMG activity in the dog.

To define the relationship between central control of upper airway muscles and respiratory muscle function, the electromyographic responses of the dilator nares muscles to stimulation of chemoreceptors and pulmonary receptors were studied in six anesthetized dogs. Only at maximal levels of hypoxia was the inspiratory activity of the dilator nares significantly increased. Hypercapnic stimulation increased the inspiratory activity with each incremental increase in CO2. Pulmonary stretch receptor stimulation produced by lung inflation inhibited dilator nares activity. Pulmonary irritant receptor stimulation by intravenously administered histamine increased dilator nares activity, as did pulmonary J receptor stimulation by the intravenous administration of capsaicin.

Animals↗
PubMed1992

Speed and profile of the arterial peripheral chemoreceptors as measured by ventilatory changes in preterm infants.

To measure the response time of the peripheral chemoreceptors, we studied 13 preterm infants [birth weight 1602 +/- 230 g (mean +/- SEM); gestational age 31 +/- 1 wk; postnatal age 15 +/- 1 d] during inhalation of 21% O2 (15 +/- 5 s) followed by 100% O2 (1 min). We used a flow-through system to measure ventilation and gas analyzers to measure alveolar gases. Hypoventilation was observed at 3.6 +/- 0.6 s and was maximal at 6.8 +/- 1 s after O2 began. This maximal response was always associated with an apnea (greater than 3 s). Alveolar PO2 increased from 13.5 +/- 0.1 kPa (101 +/- 0.8 torr) (control) to 28.0 +/- 1.2 kPa (210 +/- 9 torr) (1st O2 breath), to 42.0 +/- 2.4 kPa (315 +/- 18 torr) (1st hypoventilation), to 45.9 +/- 4.1 kPa (344 +/- 31 torr) (breath preceding maximal response), and to 53.6 +/- 4.1 kPa (402 +/- 31 torr) (at maximal response). Minute ventilation was 0.192 +/- 0.011 (control), 0.188 +/- 0.011 (1st O2 breath), 0.088 +/- 0.016 (1st hypoventilation; p less than 0.0001), 0.122 +/- 0.016 (breath preceding maximal response; p less than 0.0002), and 0.044 +/- 0.011 L/min/kg at maximal response (p less than 0.0001). This decrease in ventilation was due to a decrease in frequency with no appreciable change in tidal volume. The initial period of hypoventilation (19 +/- 4 s) was followed by a breathing interval (10 +/- 2 s) and a second period of hypoventilation (14 +/- 3 s) before continuous breathing resumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1995

Effect of drugs on chemoreceptor responsiveness in fetal sheep.

This study was designed to examine the effects of the drugs ketamine, morphine, pentobarbital, and propranolol on fetal chemoreceptor responsiveness. Eleven fetal lambs (gestational age 125-133 d) were chronically instrumented with a catheter in a hindlimb artery and vein and a forelimb artery; a carotid arterial oximeter catheter was placed in six of these fetuses. An inflatable cuff occluder was placed around the maternal hypogastric artery. Acute fetal hypoxemia was induced repeatedly by reducing uterine blood flow. Fetal heart rate, arterial pressure, and carotid arterial oxygen saturation were monitored continuously before and after administering ketamine, morphine, pentobarbital, or propranolol to the fetus. The ratio delta heart rate/delta O2 saturation has been shown previously to be a reproducible index of chemoreflex response. The differences in baseline values and changes with drugs were compared by multiple regression analysis coded by effects. Chemoreflex response was markedly attenuated by ketamine and morphine but not by pentobarbital or propranolol. Because the cardiovascular response to hypoxemia is blunted by some drugs, caution should be exercised in interpreting heart rate responses to hypoxemia in the fetus when these drugs have been administered to the mother.

Acute Disease↗
PubMed2005

Developmental changes in HIF transcription factor in carotid body: relevance for O2 sensing by chemoreceptors.

Before birth, the peripheral chemoreceptors located in the carotid bodies (CB) are adapted to the low fetal Po(2) and are relatively insensitive to hypoxia. After birth, the sensitivity of the CB to hypoxia is reset in response to the rise in Po(2). The mechanism underlying this resetting, which requires several days to complete, remains unknown. We have investigated the possibility that the hypoxia-inducible factors HIF-1alpha and HIF-2alpha, which are activated by oxygen deprivation, are involved in this resetting process. Accordingly, we used immunostaining and densitometry to quantitate the levels of the HIF-1alpha and HIF-2alpha proteins in the rat CB during early perinatal life and after exposure to in vivo hypoxia during adolescence. Tyrosine hydroxylase (TH) was used as a marker for catecholaminergic neurons and oxygen-sensitive cells in the CB. Double-immunostaining revealed constitutive expression of HIF-1alpha in both glomus cells (TH+) and sustentacular cells (TH-) of the CB of adolescent rats. However, immunoreactivity toward HIF-2alpha was restricted to glomus cells. After exposure to hypoxia (8% O(2), 6 h), the expression of HIF-1alpha was selectively up-regulated in glomus cells and apparent translocation of both HIF-1alpha and HIF-2alpha to the nucleus was observed. Both of these proteins were expressed constitutively in the CB during the perinatal transition period. During the first postnatal week, the intensity of immunostaining for HIF-1alpha in glomus cells decreased markedly, whereas the level of HIF-2alpha remained constant. We suggest that this selective down-regulation of HIF-1alpha may be involved in the postnatal maturation of CB responsiveness to hypoxia.

Active Transport, Cell Nucleus↗
PubMed2005

Non-olfactory chemoreceptors in asymmetric setae activate antennular grooming behavior in the Caribbean spiny lobster Panulirus argus.

In the spiny lobster Panulirus argus the antennules carrying olfactory sensilla called aesthetascs and several types of other non-olfactory sensilla accompanying them are frequently groomed by the third maxillipeds in a stereotyped behavioral pattern. This behavior can be elicited by chemical stimulation with l-glutamate. Using selective sensillar ablations, we tested whether this behavior is driven by the numerous aesthetascs, which have been implicated as mediating this chemically elicited antennular grooming behavior in a previous investigation, or other, less numerous sensilla called asymmetric setae, which are tightly associated with aesthetascs. The selective sensilla ablations showed that the asymmetric setae are necessary and sufficient for driving chemically elicited antennular grooming. Bilateral elimination of the ca. 160 asymmetric setae almost completely abolished the behavior, whereas bilateral elimination of the ca. 2600 aesthetascs or of another type of sensilla associated with them (guard setae) did not cause a reduction in chemically elicited antennular grooming. Microscopical analysis of the morphological properties of the asymmetric setae revealed the presence of a terminal pore at the tip of the seta and a phalloidin-positive scolopale below its base. Since these structures have been identified in decapod crustaceans as modality-specific structures of bimodal chemo- and mechanosensory sensilla, we conclude that the asymmetric setae belong to this type of sensilla and thus have the appropriate features to function as chemoreceptors in the elicitation of antennular grooming. The identification of asymmetric setae and not aesthetascs as the drivers of chemically elicited antennular grooming suggests that it is not the olfactory pathway in the brain but a parallel pathway, constituted mainly by the lateral antennular neuropils, that is the neuronal substrate of this behavior. The lateral antennular neuropils receive non-olfactory sensory input from the antennule and contain the major arborizations of antennular motoneurons, allowing that direct sensory-motor coupling is involved in mediating the chemical elicitation of antennular grooming behavior.

Analysis of Variance↗
PubMed2005

Cardiorespiratory responses to hypercarbia in tambaqui Colossoma macropomum: chemoreceptor orientation and specificity.

Experiments were carried out to test the hypothesis that ventilatory and cardiovascular responses to hypercarbia (elevated water P(CO2)) in the tambaqui Colossoma macropomum are stimulated by externally oriented receptors that are sensitive to water CO(2) tension as opposed to water pH. Cardiorespiratory responses to acute hypercarbia were evaluated in both the absence and presence of internal hypercarbia (elevated blood P(CO2)), achieved by treating fish with the carbonic anhydrase inhibitor acetazolamide. Exposure to acute hypercarbia (15 min at each level, final water CO(2) tensions of 7.2, 15.5 and 26.3 mmHg) elicited significant increases in ventilation frequency (at 26.3 mmHg, a 42% increase over the normocarbic value) and amplitude (128%), together with a fall in heart rate (35%) and an increase in cardiac stroke volume (62%). Rapid washout of CO(2) from the water reversed these effects, and the timing of the changes in cardiorespiratory variables corresponded more closely to the fall in water P(CO2) (Pw(CO2)) than to that in blood P(CO2) (Pa(CO2)). Similar responses to acute hypercarbia (15 min, final Pw(CO2) of 13.6 mmHg) were observed in acetazolamide-treated (30 mg kg(-1)) tambaqui. Acetazolamide treatment itself, however, increased Pa(CO2) (from 4.81+/-0.58 to 13.83+/-0.91 mmHg, mean +/-S.E.M.; N=8) in the absence of significant change in ventilation, heart rate or cardiac stroke volume. The lack of response to changes in blood P(CO2) and/or pH were confirmed by comparing responses to the bolus injection of hypercarbic saline (5% or 10% CO(2); 2 ml kg(-1)) into the caudal vein with those to the injection of CO(2)-enriched water (1%, 3%, 5% or 10% CO(2); 50 ml kg(-1)) into the buccal cavity. Whereas injections of hypercarbic saline were ineffective in eliciting cardiorespiratory responses, changes in ventilation and cardiovascular parameters accompanied injection of CO(2)-laden water into the mouth. Similar injections of CO(2)-free water acidified to the corresponding pH of the hypercarbic water (pH 6.3, 5.6, 5.3 or 4.9, respectively) generally did not stimulate cardiorespiratory responses. These results are in agreement with the hypothesis that in tambaqui, externally oriented chemoreceptors that are predominantly activated by increases in water P(CO2), rather than by accompanying decreases in water pH, are linked to the initiation of cardiorespiratory responses to hypercarbia.

Acetazolamide↗
PubMed2005

Spike firing allometry in avian intrapulmonary chemoreceptors: matching neural code to body size.

Biological rates in small animals are usually higher than those in large animals, yet the maximal rate of action potential (spike) generation in sensory neurons encoding rate functions is similar in all animals, due to the conserved genetics of voltage-gated ion channels. Therefore, sensory signals that vary at rates approaching maximal spike generation rate, as might occur in animals of diminished body size, may require specialized spike coding to convey this information. To test whether spike coding scales allometrically in sensory neurons monitoring signals that change frequency with body size, we recorded action potentials from 70 avian intrapulmonary chemoreceptors (IPC), respiratory neurons that detect lung CO2 changes during breathing, in five different avian species ranging in size from body mass Mb=0.045 kg (lovebirds) to 5.23 kg (geese). Since breathing frequency scales approximately to Mb-1/4 (higher in small birds, lower in large birds), we reasoned that IPC discharge frequencies may also scale to maintain spike information transmission within each breath. We found that phasic action potential discharge pattern, as quantified by the peak discharge rate and the magnitude of spike frequency adaptation, scaled between Mb-0.22 and Mb-0.26, like breathing rate (P<0.05). Previously published values of peak discharge rate in IPC also fit this allometric relationship. We suggest that mass-dependent scaling of neural coding may be necessary for preserving information transmission with decreasing body size.

Action Potentials↗
PubMed1985

Intrapulmonary chemoreceptor control of ventilatory movements in the self-ventilating chicken.

The importance of intrapulmonary chemoreceptors (IPC), sensitive to PCO2 in the lung, in the control of ventilatory movements is yet to be demonstrated in the self-ventilating bird. We distinguished between the effects of PCO2 on IPC and on extrapulmonary CO2-sensitive receptors (EPC) in anaesthetized cockerels by denervating IPC in the right lung, ligating the left pulmonary artery and changing PICO2. Left IPC were thus exposed to a combination of PCO2 from inspired gas and dead space, while EPC were exposed to greatly increased arterial PCO2 resulting from the ventilation-perfusion inequality. At 0 Torr PICO2, steady state ventilatory depth and frequency did not change (P greater than 0.5) after the ligation, although PaCO2 rose by 12.2 +/- 1.7 Torr. After the ligation, ventilatory movements were more sensitive to increasing PICO2. Tracheostomy, which results in a greater decrease in PCO2 in the innervated lung after ligation, produced greater effects. We conclude that these responses were due to the strong controlling influence of IPC on ventilatory movements in the self-ventilating cockerel.

Analysis of Variance↗
PubMed2002

Extrabranchial chemoreceptors involved in respiratory reflexes in the neotropical fish Colossoma macropomum (the tambaqui).

In a previous study, complete denervation of the gills in the tambaqui Colossoma macropomum did not eliminate the increase in breathing amplitude seen during exposure of this species to hypoxia. The present study was designed to examine other sites of putative O(2)-sensitive receptors that could be involved in this reflex action. Superfusion of the exposed brain of decerebrate, spinalectomized fish did not reveal the presence of central chemoreceptors responsive to hyperoxic, hypoxic, hypercarbic, acidic or alkaline solutions. Subsequent central transection of cranial nerve IX and X, removing not only all innervation of the gills but also sensory input from the lateral-line, cardiac and visceral branches of the vagus nerve, did not eliminate the increase in breathing amplitude that remained following peripheral gill denervation alone. Administration of exogenous catecholamines (10 and 100 nmol kg(-1) adrenaline) to fish with intact brains and minimal surgical preparation reduced both respiratory frequency and amplitude, suggesting that humoral release of adrenaline also could not be responsible for the increase in breathing amplitude that remained following gill denervation. Denervation of the mandibular branches of cranial nerve V and the opercular and palatine branches of cranial nerve VII in gill-denervated fish (either peripheral gill denervation or central section of cranial nerves IX and X), however, did eliminate the response. Thus, our data suggest that hypoxic and hyperoxic ventilatory responses as well as ventilatory responses to internal and external injections of NaCN in the tambaqui arise from O(2)-sensitive receptors in the orobranchial cavity innervated by cranial nerves V and VII and O(2)-sensitive receptors on the gills innervated by cranial nerves IX and X. Our results also revealed the presence of receptors in the gills that account for all of the increase in ventilation amplitude and part of the increase in ventilation frequency during hyperoxic hypercarbia, a group or groups of receptors, which may be external to the orobranchial cavity (but not in the central nervous system), that contribute to the increase in ventilation frequency seen in response to hyperoxic hypercarbia and the possible presence of CO(2)-sensitive receptors that inhibit ventilation frequency, possibly in the olfactory epithelium.

Animals↗
PubMed1995

Peripheral chemoreceptor function in children with myelomeningocele and Arnold-Chiari malformation type 2.

Blunted rebreathing hyperoxic hypercapnic ventilatory and arousal responses are frequent in older children with myelomeningocele (MMC) and Arnold-Chiari malformation type 2 (ACM). In contrast, isocapnic hypoxic rebreathing ventilatory responses are only occasionally affected. Thus, regions mediating the hypoxic ventilatory response appear usually preserved in children with MMC and ACM. Peripheral chemoreceptor function (PCR), however, has not been critically assessed in these children. To study this, PCR was measured in ten children and adolescents with MMC and ACM with normal alveolar ventilation during wakefulness, and in ten sex- and age-matched controls by measuring the ventilatory responses induced by 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 15% CO2 in O2. In general, tidal breathing of 100% O2 resulted in smaller decreases in minute ventilation (VE) responses in patients with MMC, although absent VE responses to hyperoxia were found in four patients. Vital capacity breaths of 15% CO2 elicited similar increases in VE in five patients and in ten controls, but no changes in VE were found in the remaining five patients (p < 0.02). Acute hypoxia induced by N2 tidal breathing resulted in significant linear regression correlations between VE and SpO2 in five patients with MMC, while absent responses were measured in those same five patients with absent hypercapnic responses. We conclude that PCR, when assessed by acute hypoxia, hyperoxia, or hypercapnia is abnormal in some children with MMC and ACM, particularly in those demonstrating abnormal ventilation during sleep. We postulate that the large interindividual variability of PCR is dependent on the severity of brainstem involvement of PCR afferents or central respiratory integration sites.

Adolescent↗
PubMed2004

High genetic diversity in the chemoreceptor superfamily of Caenorhabditis elegans.

We investigated genetic polymorphism in the Caenorhabditis elegans srh and str chemoreceptor gene families, each of which consists of approximately 300 genes encoding seven-pass G-protein-coupled receptors. Almost one-third of the genes in each family are annotated as pseudogenes because of apparent functional defects in N2, the sequenced wild-type strain of C. elegans. More than half of these "pseudogenes" have only one apparent defect, usually a stop codon or deletion. We sequenced the defective region for 31 such genes in 22 wild isolates of C. elegans. For 10 of the 31 genes, we found an apparently functional allele in one or more wild isolates, suggesting that these are not pseudogenes but instead functional genes with a defective allele in N2. We suggest the term "flatliner" to describe genes whose functional vs. pseudogene status is unclear. Investigations of flatliner gene positions, d(N)/d(S) ratios, and phylogenetic trees indicate that they are not readily distinguished from functional genes in N2. We also report striking heterogeneity in the frequency of other polymorphisms among these genes. Finally, the large majority of polymorphism was found in just two strains from geographically isolated islands, Hawaii and Madeira. This suggests that our sampling of wild diversity in C. elegans is narrow and that identification of additional strains from similarly isolated regions will greatly expand the diversity available for study.

Alleles↗
PubMed1988

Effect of cisternal administration of acetazolamide on rapid excitation of central chemoreceptors.

We evaluated rapid and transient changes in phrenic (PN) and internal intercostal (IIC) activities when 0.5 ml of saline saturated with 100% CO2 was injected into the vertebral artery at the C1 level before and after cisternal administration of carbonic anhydrase inhibitor (acetazolamide) in decerebrated, spontaneously breathing cats. Before acetazolamide administration, the injections evoked an initial, transient inhibition of ongoing PN or IIC activity, followed by excitation of subsequent respiratory activities with a short onset latency of less than 3 sec. On the other hand, cisternal administration of acetazolamide abolished both the initial inhibition and the subsequent rapid excitation of respiratory activities, although there still existed a delayed, weak and prolonged excitation of respiration. These results indicated that hydration of CO2 accelerated by carbonic anhydrase within the brain would be essential for the rapid changes in respiratory activity mediated by the central chemoreceptors.

Acetazolamide↗
PubMed1986

Effects of carotid chemoreceptor stimulating and depressing agents on internal intercostal muscle activity in the rabbit.

The effects of carotid chemoreceptor stimulating and depressing agents on internal intercostal muscle activity (IIMA) were studied before and after surgical denervation of the carotid sinus nerve (CSN) in the rabbit. An intracarotid injection of 30 micrograms of sodium cyanide (NaCN) during inspiration caused an increase in both IIMA and respiratory rate (RR). In contrast, intracarotid administration of 10 micrograms of dopamine (DA) during inspiration resulted in a decrease in both IIMA and RR. The NaCN- and DA-induced characteristic responses in IIMA were abolished by the section of the CSN. The results indicate that the excitatory and inhibitory responses of IIMA to intracarotid injections of NaCN and DA are mainly mediated through carotid chemoreflexes.

Animals↗
PubMed1984

[Technical difficulties raised by the suppression of ventilatory responses from peripheral chemoreceptors in the rat].

In normal pentobarbitalized Wistar rats, simultaneous section of Hering nerves and resection of superior cervical sympathetic chain, suppress chemosensibility, in 50% cases: ventilatory responses to cyanide and to hypoxia are completely suppressed by the surgical denervation. Vagotomy completes loss of chemosensibility in a few animals, indicating the presence of intrathoracic chemoreceptors of minor importance. Local anaesthesia with lidocaïne of extra craniobasal unidentified structures, is as effective as surgical chemodenervation for suppressing ventilatory responses. This technic is not suitable for experimental purposes in long duration assays.

Animals↗
PubMed1986

Relation between peripheral chemoreceptors stimulation and pulmonary arterial blood pressure in rats.

As interactions between peripheral chemoreceptors stimulation (PCS) and pulmonary vasomotor tone remain controversial, experiments were made in rats in order to clear up the effects of PCS on pulmonary arterial pressure (PAP). Different stimulations varying in intensities were used, in rats nervously intact (IR-rats), after vagotomy (XT-rats), after chemodenervation obtained without vagotomy (CDN not XT-rats) or with XT (CDN + XT) and finally after alpha 1-receptors blockade (P-rats = pretreated rats). The observed variations were analysed in view of disentangling reflex part of PCS from a direct activity on the pulmonary vascular bed. Ventilation, PAP and systemic blood pressure (BP) were studied in anaesthetized rats. N2 test, NaCN test, 20 s of 5% O2 inhalation and almitrine bismesylate (ALM) were used as PCS, ranged in the order of their relative intensities, from the ventilatory responses observed in IR-rats. In IR-rats, N2-and CN test produced a similar transient increase of PAP, slightly more extended than the hyperventilation. After XT, the responses were prolonged, but amplified only in CN test. Ventilatory responses disappear after CDN, but as far as pulmonary hypertension is concerned, CDN + XT is more potent than CDN without XT to reduce or even suppress them. This fact is particularly evident with ALM who is the strongest PCS used. Similar reduction of PAP rise was also produced in P-rats in which ventilatory responses remain unchanged. Prolonged hypoxic inhalation induced a progressive fall of systolic BP and of PAP. The return to normal air breathing is followed by BP restoration and a long-lasting PAP increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Almitrine↗
PubMed2000

Cardiac and pulmonary vagal neurons receive excitatory chemoreceptor input.

The effects of hypercapnia and hypocapnia on the activities of the cardiac and pulmonary vagal single fibers were examined in the decerebrated, unanesthetized, paralyzed, and vagotomized cats. The animals breathed 100% O2. Fractional end tidal CO2 concentration was raised to 9% by adding CO2 into the O2 inlet. Average discharge rate of efferent cardiac vagal units (n=10) increased from 1.0+/-0.3 to 2.2+/-0.3 Hz. Hypocapnia apnea was produced by hyperventilation. Activities of cardiac vagal units tested (n = 4) showed dramatic decrease (0.1+/-0.0 Hz). Mean arterial blood pressure did not change significantly under these conditions. In contrast, only instantaneous firing rate during inspiration was significantly increased for efferent pulmonary vagal units (n = 11) during hypercapnia. The activities of the 3 pulmonary vagal units tested with hypocapnia decreased significantly. We concluded that cardiac and pulmonary vagal neurons were excited by chemoreceptor input.

Animals↗
PubMed1976

Respiratory and circulatory reflexes induced by nicotine injections: role of carotid body chemoreceptors.

Intravenous and intracarotid injections of nicotine were delivered to cats anesthetized with pentobarbital. Low doses of nicotine were found to induce reflex hyperventilation and hypertension, mainly due to excitation of carotid body chemoreceptors. The frequency of discharge of carotid nerve chemosensory fibres was increased by nicotine in doses as low as 1 mug/kg when injected intravenously and 50 ng when injected into the carotid artery. Nicotine also activates vagal afferent fibres; some of them produce reflex excitation of the respiratory and vasomotor centres, but others provoke reflex inhibition. High doses of nicotine can act directly upon the medulla provoking acceleration or arrest of ventilation. Nicotine can also induce 'late' changes of b.p. (delay 5 sec or more) which are not mediated by the carotid or vagus nerves.

Acetylcholine↗
PubMed1976

Chemoreceptor function and sleep state in apnea.

Resting ventilation and ventilatory responses to 100% oxygen and to 5% carbon dioxide in air were measured in REM and non-REM sleep in post-neonatal infants. Normal controls were compared to infants with prolonged apnea and to siblings of sudden infant death victims. No significant differences in ventilatory responses were found between the groups. We conclude that apnea may occur in infants whose central and peripheral chemoreceptor activity is normal while they are breathing.

Apnea↗