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PubMed1995

Chemoreceptor-sensitive neurons in commissural subnucleus of nucleus tractus solitarius of the rat.

Experiments were carried out in pentobarbital-anesthetized, vagotomized, paralyzed, and artificially ventilated male Wistar rats with a pneumothorax. Blood pressure, heart rate, and phrenic nerve activity were recorded. Extracellular neuronal recordings were made by glass micropipettes in a midline area in the commissural subnucleus of the nucleus tractus solitarius. At the end of the experiment, the recording sites were marked. Chemoreceptors were stimulated by tracheal administration of N2 or injection of CO2-saturated saline (50 microliters) near the carotid body. The baroreceptors were stimulated by an intravenous injection of phenylephrine (1-3 micrograms). Neurons that were excited by chemoreceptor stimulation but not baroreceptor stimulation were found in the commissural subnucleus of nucleus tractus solitarius and were designated as chemoreceptor-sensitive neurons. They exhibited a continuous discharge (9.9 +/- 1.3 spikes/s) that showed no apparent relation to either phrenic nerve bursts or arterial pulses. Such neurons were not found in the rostral portions of the nucleus tractus solitarius. These results confirm and extend our previous reports in which a discrete chemoreceptor projection site was identified in the commissural subnucleus of the rat.

Animals↗
PubMed1975

Role of peripheral and central chemoreceptors in the initiation of fetal respiration.

The relationship between fetal femoral arterial P02 and PC02 was evalulated in 13 fetal sheep with intact and denervated peripheral chemoreceptors. With intact chemoreceptors, a significant relationship was found between fetal Pa02 and PaC02 at the time of the first breath (Pa02 = 2.57 + 0.09 PaC02; r = 0.62, P less than 0.05)mfollowing bilateral carotid sinus nerve section (CSN) or total peripheral chemodenervation (TD), PaC02. Comparison of the intact, CSN, and TD blood gases at the time of the first breath demonstrated that a) severe hypoxemia stimulates fetal respiration even following total peripheral chemodenervation; b) fetal central chemoreceptors do not respond to PaC02; c) PaC02 acting via peripheral chemoreceptors has a minor modulating effect on the degree of hypoxemia required to initiate fetal respiration. At a PaC02 below 40 mmHg this effect is inhibitory, acting via the carotid body. At a PaC02 above 90 mmHg this effect is stimulatory, acting via both carotid and aortic bodies.

Animals↗
PubMed1982

Chemoreceptor involvement in cortisol responses to hypoxia in ventilated dogs.

Changes in cortisol secretion rate (CSR) in response to hypoxic hypoxia (HH) and to carbon monoxide hypoxia (COH) were assessed in mongrel dogs that had intact chemoreceptors (INT); surgically deafferented carotid bodies (CBD) or aortic bodies (ABD); or both carotid and aortic chemoreceptors denervated (SAD). All dogs were anesthetized, paralyzed, ventilated, and maintained normocapnic. In the INT and ABD groups, CSR responded "maximally" to HH, whereas in CBD and SAD animals, the CSR was attenuated but not eliminated. COH, which does not stimulate the carotid body, caused a submaximal increase in CSR regardless of chemoreceptor status. It is concluded that 1) the carotid bodies are the principal chemoreceptor influence on CSR during HH and 2) there is a nonchemoreceptor-mediated increase in CSR during hypoxia.

Adrenal Cortex↗
PubMed1982

Central and peripheral chemoreceptor inputs to phrenic and hypoglossal motoneurons.

We tested the hypothesis that phrenic and hypoglossal responses to progressive hypercapnia differ qualitatively because the CO2-related drive inputs to their respective motoneuron pools are different. The relative contributions of carotid sinus and central chemoreceptor inputs to hypoglossal and phrenic responses during hyperoxic hypercapnia were determined by comparing the two nerve activities during rebreathing runs done either before and after bilateral carotid sinus nerve (CSN) section, or without and with cooling of the intermediate, I(s), area on the ventral surface of the medulla. The studies were performed on chloralose-anesthetized, vagotomized, paralyzed cats. Cooling of the I(s) area impaired phrenic responsiveness to hypercapnia more than hypoglossal responsiveness, whereas CSN section had the opposite effect. Thus phrenic nerve response was more dependent on central chemoreceptor input than was the hypoglossal response, but hypoglossal response was more dependent on carotid sinus chemoreceptor input. We conclude that the phrenic and hypoglossal motoneuron pools each receive a different functional input from both the medullary and the carotid sinus chemoreceptors.

Action Potentials↗
PubMed1984

Central-peripheral chemoreceptor interaction in awake cerebrospinal fluid-perfused goats.

We assessed the ventilatory interaction between central [central nervous system (CNS)] and peripheral chemoreceptor stimuli in five awake goats. CNS extracellular fluid (ECF) [H+] was altered with cisterna magna perfusion of mock CSF. Peripheral chemoreceptors were stimulated with three doses of NaCN given intravenously. The resulting dose-response curves were used to assess interaction of the central and peripheral stimuli. The observed interaction was hypoadditive; i.e., the average slope of the NaCN-inspired minute ventilation dose-response line was significantly greater during alkaline perfusion than during acidic perfusion. This correlation can be described by slope = -0.24 (CSF [H+]) + 30.7; r = 0.67 (P less than 0.01). Increased ventilatory responses were accompanied by increases in mean inspiratory flow, tidal volume, and breathing frequency and decreases in expiratory time in response to peripheral chemoreceptor stimulation. Unlike previous reports in anesthetized and denervated animals, in our awake intact goats the ventilatory and tidal volume responses showed no significant dependence on the level of control (pre-NaCN stimulus) inspired minute ventilation. We conclude that the level of [H+] in cerebral ECF exerts a significant reflex-mediated hypoadditive effect on the ventilatory responses to peripheral chemoreceptor stimulation.

Animals↗
PubMed1990

Cobalt stimulates carotid body chemoreceptors.

Because cobalt administration is known to elicit erythropoietin response, it is a reasonable hypothesis that cobalt would also stimulate the O2-sensing process in the peripheral chemoreceptors. We tested this hypothesis by measuring the effects of cobalt chloride on carotid chemosensory fibers in pentobarbital-anesthetized cats that were paralyzed and artificially ventilated. Responses of carotid chemoreceptor afferents to graded doses of cobalt given by intra-arterial injections (0.08-2.10 mumols) were measured at constant blood gases. Responses of the same chemoreceptor afferents to hypoxia, before and after a saturation dose of cobalt, were measured. In two experiments carotid body tissue PO2 was also simultaneously measured. The chemosensory fibers showed prolonged excitation after a brief period of inhibition subsequent to cobalt administration. The stimulatory effect showed a dose-dependent saturation response. Cobalt augmented rather than blocked carotid chemoreceptor response to hypoxia. The effect of cobalt was not mediated by tissue PO2. These results are consistent with the hypothesis that cobalt stimulates the O2-sensing mechanism, although a direct effect of cobalt on the excitability of the chemosensory terminal remains a possibility.

Animals↗
PubMed1990

Two discharge patterns of carotid body chemoreceptors in the goat.

Twenty-nine single carotid body chemoreceptor units recorded during normocapnic normoxia from 20 anesthetized goats were classified into two groups by discharge pattern. Thirteen fibers, which had interspike interval distributions with a prominent peak [24.0 +/- 9.8% (SD)] at 0- to 20-ms bin, were termed bursting fibers (BF). The 16 remaining fibers were termed nonbursting fibers (NBF); these had no notable peak in the interval distributions. During hypoxia and hypercapnia, the chemoreceptor fibers continued to discharge in their established patterns. The interval distribution of most NBF spike trains could be described with the Poisson process, but none of the BF could be. However, except for the intervals in the range of 0-20 ms, the interval distribution of the BF could be described as exponential. This study suggests that 1) there are two distinct populations of the goat chemoreceptor fiber, each with an inherent discharge pattern; 2) the chemoreceptor did not code information about arterial PO2 and PCO2 in different patterns; and 3) the basic chemotransduction mechanism is likely the same in BF and NBF, and the difference in discharge pattern is more likely to reflect processes downstream from the transducer.

Action Potentials↗
PubMed1991

Dynamic ventilatory responses to CO2 in the awake lamb: role of the carotid chemoreceptors.

In awake lambs we investigated the role of the peripheral chemoreceptors in producing dynamic ventilatory (VE) responses to CO2. The immediate VE response, within 15 s, to transient CO2 inhalation was studied in two groups: 1) five lambs before carotid denervation and 2) the same lambs after carotid denervation. The time course of VE responses during the first 60 s after a step change to 8% inspired CO2 was also studied in lambs after carotid denervation and in a group of six carotid body-intact lambs 10-11 days of age. Acute CO2 responses were assessed using step changes to various concentrations of CO2 + air and CO2 + O2, while VE was recorded breath by breath. Intact lambs exhibited a brisk VE response to step changes in CO2, beginning after 3-5 s. Hyperoxia altered but did not suppress the dynamic VE CO2 response when the carotid chemoreceptors were intact. Carotid denervation markedly reduced the VE response during the first 25 s after a CO2 step change, revealing the time delay required for the central chemoreceptors to produce an effective VE response. The residual VE response remaining after CD was thought to be mediated by the remaining aortic body chemoreceptors and was eliminated by adding O2 to the CO2 challenges. However, after carotid denervation, even with CO2 + hyperoxia, the onset of a small tidal volume response was apparent by 10-12 s.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Peripheral chemoreceptors respond to hypoxia in pontine-lesioned fetal lambs in utero.

Acute hypoxia inhibits, rather than stimulates, fetal breathing movements (FBM), but there has been controversy as to the activity and role of the peripheral arterial chemoreceptors in the regulation of breathing movements in the unanesthetized fetus in utero. However, after midcollicular brain stem transection or lateral pontine lesion, hypoxia causes FBM to become continuous and stimulated in rate and depth. To determine whether this stimulatory response involves peripheral chemoreceptors, we used a two-stage approach to examine the response to hypoxia after peripheral chemodenervation in lateral pontine-lesioned fetal lambs. The lateral pons was lesioned at 119-121 days, and the response to hypoxia was tested in the unanesthetized fetus 4 days afterward. Fourteen fetuses in which hypoxia stimulated FBM underwent either peripheral chemodenervation or sham denervation in a second operation. Hypoxia had no effect when the fetus was tested 4-5 days after peripheral chemodenervation, and the basal incidence of FBM was significantly lower. The stimulatory response was unchanged by sham denervation. We conclude that the peripheral chemoreceptors are active in fetal life and that they mediate the stimulation of FBM seen in response to hypoxia after removal of the lateral pontine inhibition. In addition, after pontine lesion there is evidence of tonic chemoreceptor-mediated influences on FBM, which are normally overriden in the intact fetus.

Animals↗
PubMed1994

Effect of chemoreceptor stimulation and inhibition on total pulmonary resistance in humans during NREM sleep.

We investigated the effect of chemoreceptor stimulation and inhibition on total pulmonary resistance (RL) during non-rapid-eye-movement (NREM) sleep in healthy subjects. Chemoreceptor stimulation was accomplished with brief isocapnic hypoxia (n = 8). Minute ventilation increased to 150% of room air control. RL at peak inspiratory flow decreased to 66% of room air control. Resistive pressure-inspiratory flow plots demonstrated lower resistive pressures for a given inspiratory flow. Chemoreceptor inhibition was accomplished by abruptly terminating brief hypocapnic hypoxia with 100% O2 (n = 7). Minute ventilation decreased to 63% of room air control. RL calculated at peak inspiratory or fixed flow did not change significantly, and pressure-flow plots at nadir ventilation showed no systematic change from room air control. We conclude that 1) hypoxic chemoreceptor stimulation is associated with decreased RL and enhancement of pressure-flow relationships, suggesting increased upper airway caliber; 2) upper airway patency is not compromised during periods of low ventilatory drive in normal subjects; and 3) upper airway dilating muscles and thoracic pump muscles are optionally coordinated with increased and decreased ventilatory drive.

Adult↗
PubMed2004

Cannabinoid receptor expression in peripheral arterial chemoreceptors during postnatal development.

Prenatal exposure to tobacco smoke increases risk of sudden infant death syndrome (SIDS). Marijuana is frequently smoked in conjunction with tobacco, and perinatal exposure to marijuana is associated with increased incidence of SIDS. Abnormalities in peripheral arterial chemoreceptor responses during sleep may be operative in infants at risk for SIDS, and nicotine exposure adversely affects peripheral arterial chemoreceptor responses. To determine whether marijuana could potentially affect the activity of peripheral arterial chemoreceptors during early postnatal development, we used in situ hybridization histochemistry to characterize the pattern and level of mRNA expression for cannabinoid type 1 receptor (CB1R) in the carotid body, superior cervical ganglia (SCG), and nodose-petrosal-jugular ganglia (NG-PG-JG) complex in newborn rats. We used immunohistochemistry and light, confocal, and electron microscopy to characterize the pattern of CB1R and tyrosine hydroxylase protein expression. CB1R mRNA expression was intense in the NG-PG-JG complex, low to moderate in the SCG, and sparse in the carotid body. With maturation, CB1R gene expression significantly increased (P < 0.01) in the NG-PG-JG complex. CB1R immunoreactivity was localized to nuclei of ganglion cells in the SCG and NG-PG-JG complex, whereas tyrosine hydroxylase immunoreactivity was localized to the cytoplasm. Exposure to marijuana during early development could potentially modify cardiorespiratory responses via peripheral arterial chemoreceptors. The novel finding of nuclear localization of CB1Rs in peripheral ganglion cells suggests that these receptors may have an, as yet, undetermined role in nuclear signaling in sensory and autonomic neurons.

Animals↗
PubMed2004

Effect of caffeine on peripheral chemoreceptor activity in premature neonates: interaction with sleep stages.

Caffeine is widely used for the treatment of apnea in premature neonates. However, the localization of caffeine's target site (central nervous system and/or peripheral chemoreceptors) is not well defined, especially for sleeping neonates whose sleep stages interact with respiratory control. The aim of this study was to assess the activity of the peripheral chemoreceptors in relation to sleep stages in premature neonates treated (or not) with caffeine for idiopathic apnea. Peripheral chemoreceptor activity was assessed in 22 neonates (postconceptional age of 36 +/- 1 wk with birth weights ranging from 790 to 1,910 g) by performing a 30-s hyperoxic test during active and quiet sleep. Eleven neonates received caffeine treatment (4.0 +/- 0.5 mg.kg(-1).day(-1)) and 11 served as controls. For all neonates, the decrease in minute ventilation observed during hyperoxia was greater during active than during quiet sleep. Neonates receiving caffeine showed a significantly greater decrease in ventilation during hyperoxia in both sleep stages, compared with controls (caffeine; -29.7 +/- 12.8% vs. control; -22.0 +/- 7.4%; F(1,15) = 4.6, P = 0.04). We conclude that caffeine administration increases the effectiveness of chemoreceptor activity. Because sleep stage durations were not affected by the treatment, it is likely that the decrease in apneic episodes typically observed with caffeine therapy is only related to respiratory processes and is independent of the sleep stage organization.

Birth Weight↗
PubMed1979

Baroreceptor and chemoreceptor responses to umbilical cord occlusion in fetal lambs.

11 fetal lambs with gestational age of 116-135 days were studied while connected to a membrane-oxygenator replacing the ventilatory function of the placenta. Progressive increase in arterial oxygen tension from 20 to 220 mm Hg resulted in progressive decrease in baseline heart rate and baseline arterial blood pressure indicating presence of chemoreceptor activity over this wide range of arterial oxygen tension. The effect of 60 sec complete umbilical cord occlusion was studied at progressively higher arterial oxygen tension and it was concluded that the chemoreceptor activity at fetal normoxic condition is very brisk and is markedly attenuated at hyperoxic levels. Although it was not possible to completely separate baroreceptor and chemoreceptor reflexes involved in cardiovascular response to umbilical cord occlusion, it is postulated that the chemoreceptor and baroreceptor reflexes are complimentary during cardiovascular responses to umbilical cord occlusion.

Animals↗
PubMed1994

Mechanisms of apnea termination in obstructive sleep apnea. Role of chemoreceptor and mechanoreceptor stimuli.

Previous work from our laboratory has indicated that mechanoreceptor feedback from the respiratory muscles may play an important role in arousal and apnea termination in obstructive sleep apnea (OSA). Other studies have pointed to a prominent role for chemoreceptor stimuli. We postulated that mechanoreceptor stimuli from the respiratory system are the primary determinant of apnea termination, and that chemoreceptor stimuli exert their effect indirectly through stimulation of ventilation and thus proprioceptive feedback. To test this, we measured the diaphragmatic tension-time index (TTdi) during obstructive sleep apneas in seven male subjects with severe untreated OSA. We compared the maximal TTdi values at end-apnea during administration of air, O2, and CO2. We reasoned that if mechanoreceptor stimuli mediate apnea termination, changing the degree of chemoreceptor stimulation during apneas should not alter the level of respiratory effort at end-apnea. O2 administration produced a significant increase in end-apneic arterial oxygen saturation (SaO2) and increased apnea duration. CO2 administration led to an increase in pre- and postapneic end-tidal carbon dioxide pressure (PETCO2), and tended to shorten apneas. However, the mean value for maximal end-apneic TTdi was 0.12 +/- 0.01 (SEM) during room air breathing and was unaltered by O2 (0.12 +/- 0.01) or CO2 (0.11 +/- 0.01) administration. The consistency of end-apneic TTdi values despite the varying chemical drive supports the hypothesis that apnea termination in OSA is mediated by mechanoreceptor feedback from the respiratory system, most likely from the respiratory muscles. The influence of chemoreceptor information may be mediated indirectly through an effect on ventilatory effort.

Adult↗
PubMed1991

Interaction of baroreceptor and chemoreceptor reflex control of sympathetic nerve activity in normal humans.

Animal studies have demonstrated that activation of the baroreflex by increases in arterial pressure inhibits cardiovascular and ventilatory responses to activation of peripheral chemoreceptors (PC) with hypoxia. In this study, we examined the influences of baroreflex activation on the sympathetic response to stimulation of PC and central chemoreceptors in humans. PC were stimulated by hypoxia (10% O2/90% N2) (n = 6) and central chemoreceptors by hypercapnia (7% CO2/93% O2) (n = 6). Responses to a cold pressor stimulus were also obtained as an internal reflex control to determine the selectivity of the interactive influence of baroreflex activation. Baroreflex activation was achieved by raising mean blood pressure by greater than 10 mmHg with intravenous infusion of phenylephrine (PE). Sympathetic nerve activity (SNA) to muscle was recorded from a peroneal nerve (microneurography). During hypoxia alone, SNA increased from 255 +/- 92 to 354 +/- 107 U/min (P less than 0.05). During PE alone, mean blood pressure increased and SNA decreased to 87 +/- 45 U/min (P less than 0.05). With hypoxia during baroreflex activation with PE, SNA did not increase (50 +/- 23 U/min). During hypercapnia alone, SNA increased from 116 +/- 39 to 234 +/- 72 U/min (P less than 0.01). Hypercapnia during baroreflex activation with PE increased SNA from 32 +/- 25 U/min during PE alone to 61 +/- 26 U/min during hypercapnia and PE (P less than 0.05). Like hypercapnia (but unlike hypoxia) the cold pressor test also increased SNA during PE. We conclude that baroreflex activation selectively abolishes the SNA response to hypoxia but not to hypercapnia or the cold pressor test. The inhibitory interaction of the baroreflex and the peripheral chemoreflex may be explained by convergence of baroreceptor and peripheral chemoreceptor afferents on neurons in the medulla.

Adult↗
PubMedDate not supplied

Laryngeal regulation of airway resistance. I. Chemoreceptor reflexes.

The resistance of the larynx to airflow was measured during hypercapnia, hypoxemia, and stimulation of peripheral chemoreceptors by sodium cyanide and phenyl diguanide in 15 dogs anesthetized with alpha-chloralose (80 mg/kg). Laryngeal airway resistance (R1x) was obtained by measuring the pressure difference between the subglottic region and the mouth while a constant flow of humidified air was passed through the larynx. During spontaneous respiration, R1x varies with the phase of the respiratory cycle: R1x is high during expiration (mean +/- SEM = 0.79 +/- 0.19 cm H2O/L/sec) and falls just before inspiration (0.49 +/- 0.14 cm H2O/L/sec) and remains low until the end of inspiration. Hypercapnia, hypoxemia, and chemoreceptor stimulation each stimulated respiration and simultaneously decreased R1x during both inspiration and expiration. Chemoreceptor stimulation with phenyl diguanide (100 microgram/kg) and sodium cyanide (100 microgram/kg) produced similar decreases in R1x whether injected into the right atrium or left ventricle, indicating that these agents are not stimulating pulmonary receptors. The decrease in R1x during stimulation of chemoreceptors will decrease the work of ventilation. This study suggests that the control of ventilation involves the active regulation of the resistance of the laryngeal airway.

Airway Resistance↗
PubMedDate not supplied

Response of laryngeal airway resistance to chemoreceptor stimulation: effect of pulmonary afferent denervation.

The response of laryngeal airway resistance to chemoreceptor stimulation was measured before and after vagotomy in ten anesthetized dogs. With the vagus nerves intact, stimulation of chemoreceptors produced a decrease in both inspiratory and expiratory laryngeal resistance. After bilateral vagotomy below the origin of the recurrent laryngeal nerves, stimulation of chemoreceptors produced a smaller decrease in inspiratory laryngeal resistance and an increase in expiratory laryngeal resistance. We concluded that pulmonary afferent input to the respiratory neurons maintains a low airway resistance during chemoreceptor stimulation.

Afferent Pathways↗
PubMed2006

Chemoreceptor plasticity and respiratory acclimation in the zebrafish Danio rerio.

The goals of this study were to assess the respiratory consequences of exposing adult zebrafish Danio rerio to chronic changes in water gas composition (hypoxia, hyperoxia or hypercapnia) and to determine if any ensuing effects could be related to morphological changes in branchial chemoreceptors. To accomplish these goals, we first modified and validated an established non-invasive technique for continuous monitoring of breathing frequency and relative breathing amplitude in adult fish. Under normal conditions 20% of zebrafish exhibited an episodic breathing pattern that was composed of breathing and non-breathing (pausing/apneic) periods. The pausing frequency was reduced by acute hypoxia (Pw(O)2<130 mmHg) and increased by acute hyperoxia (Pw(O)2>300 mmHg), but was unaltered by acute hypercapnia. Fish were exposed for 28 days to hyperoxia (Pw(O)2>350 mmHg), or hypoxia (Pw(O)2=30 mmHg) or hypercapnia (Pw(CO)2=9 mmHg). Their responses to acute hypoxia or hypercapnia were then compared to the response of control fish kept for 28 days in normoxic and normocapnic water. In control fish, the ventilatory response to acute hypoxia consisted of an increase in breathing frequency while the response to acute hypercapnia was an increase in relative breathing amplitude. The stimulus promoting the hyperventilation during hypercapnia was increased Pw(CO)2 rather than decreased pH. Exposure to prolonged hyperoxia decreased the capacity of fish to increase breathing frequency during hypoxia and prevented the usual increase in breathing amplitude during acute hypercapnia. In fish previously exposed to hyperoxia, episodic breathing continued during acute hypoxia until Pw(O)2 had fallen below 70 mmHg. In fish chronically exposed to hypoxia, resting breathing frequency was significantly reduced (from 191+/-12 to 165+/-16 min(-1)); however, the ventilatory responses to hypoxia and hypercapnia were unaffected. Long-term exposure of fish to hypercapnic water did not markedly modify the breathing response to acute hypoxia and modestly blunted the response to hypercapnia. To determine whether branchial chemoreceptors were being influenced by long-term acclimation, all four groups of fish were acutely exposed to increasing doses of the O(2) chemoreceptor stimulant, sodium cyanide, dissolved in inspired water. Consistent with the blunting of the ventilatory response to hypoxia, the fish pre-exposed to hyperoxia also exhibited a blunted response to NaCN. Pre-exposure to hypoxia was without effect whereas prior exposure to hypercapnia increased the ventilatory responses to cyanide. To assess the impact of acclimation to varying gas levels on branchial O(2) chemoreceptors, the numbers of neuroepithelial cells (NECs) of the gill filament were quantified using confocal immunofluorescence microscopy. Consistent with the blunting of reflex ventilatory responses, fish exposed to chronic hyperoxia exhibited a significant decrease in the density of NECs from 36.8+/-2.8 to 22.7+/-2.3 filament(-1).

Adaptation, Physiological↗