Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Chemoreceptor”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

Static and dynamic responses of renal chemoreceptor neurons to intrapelvic pressure increases in the rat.

Multiunit afferent renal nerve activity (ARNA) and single unit activity from R2 chemoreceptors were recorded in anesthetized male Sprague Dawley rats during rapid and graded increases in intrapelvic pressure. Multiunit ARNA in 9 rats was excited by rapid intrapelvic pressure increases to 20 mmHg with non-diuretic urine (285.5 +/- 76.2% above control) but not when isotonic saline was used to fill the pelvis (13.0 +/- 9.0%). Similar responses were recorded from 27 single R2 chemoreceptors. Multiunit ARNA showed a direct, linear relationship with ramp increases in intrapelvic pressure between 0 and 20 mmHg at rates of 0.05, 0.15 and 0.3 mmHg/s. The responses were dynamically linked to intrapelvic pressure and maximum activations showed a positive linear relationship with the rate of pressure increase. Individual R2 chemoreceptor activity showed a similar dynamic relationship with intrapelvic pressure. ARNA was also excited by intrapelvic backflow of diuretic urine (10% expansion of extracellular volume) but the response in impulses/s was depressed by 58.6 +/- 9% in multiunit preparations and 30.1 +/- 10.8% for R2 chemoreceptors. Basal activities were also reduced during diuresis by 49.0 +/- 16% and 36.7 +/- 12.3% for multiunit and single unit preparations, respectively, and the percent increases over background during urine backflow were not different in non-diuresis and diuresis. Both multiunit ARNA and R2 chemoreceptors were also activated by ramp increases in intrapelvic pressure during diuresis, but the dynamic component was lost and responses to each pressure ramp were not different. The similarity in responses between multiunit ARNA and individual R2 chemoreceptors indicates that the multiunit ARNA activation during intrapelvic pressure increases is largely composed of activity from R2 chemoreceptors.

Animals↗

Reflex response and convergence of pharyngoesophageal and peripheral chemoreceptors in the nucleus of the solitary tract.

The pharynx is a common conduit for the passage of both ingested material and respiratory gases and may receive a dual control from medullary structures regulating deglutition and respiration. We sought both to compare the pattern of reflex response following stimulation of pharyngoesophageal and peripheral chemoreceptors and to assess whether these afferents converge in the nucleus of the solitary tract. In an arterially perfused working heart-brainstem preparation of mature rat, pharyngoesophageal receptors were stimulated by distension of the pharyngeal-oesophageal junction, whereas chemoreceptors were activated by sodium cyanide solution. In peripheral studies we recorded electromyographic activity from genioglossus, mylohyoideus and the lower thoracic oesophagus as well as hypoglossal, laryngeal and phrenic motor discharge. Sub-glottal pressure was also measured at constant airflow. In central studies, nucleus of the solitary tract neurons were recorded with blind whole-cell techniques. In peripheral studies spontaneous irregular electromyographic discharges (cycle length 99+/-26 s) occurred sequentially in genioglossus and mylohyoideus muscles (during the inter-phrenic nerve activity interval) and subsequently the oesophagus; these were accompanied by post-inspiratory discharges in both hypoglossal and laryngeal motor nerves and an atropine-sensitive bradycardia (-39+/-5 beats/min). Components of the reflex response elicited following stimulation of both pharyngoesophageal receptors and chemoreceptors were qualitatively similar and included: (i) expiratory-related increases in laryngeal pressure; (ii) sequential electromyographic discharge in genioglossus, mylohyoideus muscles and oesophagus; (iii) post-inspiratory burst discharge in hypoglossal, recurrent and superior laryngeal motor nerves; and (iv) an atropine-sensitive bradycardia (-38 to -95 beats/min). The chemoreceptor reflex-evoked responses were abolished after sinoaortic denervation. Of 135 whole-cell recordings of nucleus of the solitary tract neurons, 31 received a synaptic input from pharyngoesophageal receptors (22 excitatory and nine inhibitory). Cells excited by pharyngoesophageal receptor stimulation were either "spontaneously" bursting, which occurred during the inter-phrenic nerve activity interval (cycle length 79+/-22 s; n=9), or non-bursting (n=13). Of the 22 nucleus of the solitary tract neurons excited by pharyngoesophageal receptor stimulation, 77% received a convergent excitatory synaptic input from chemoreceptors (eight bursting and nine non-bursting neurons). Thus, stimulation of pharyngoesophageal receptors and chemoreceptors evoked common reflex response components including activation of hypoglossal, laryngeal adductor, cardiac vagal motoneurons and swallowing. Moreover, some excitatory pharyngoesophageal and chemoreceptors inputs typically converged on nucleus of the solitary tract neurons. The possibility that this convergence manifests a defensive reflex reaction is discussed.

Animals↗

Carotid body chemoreceptor function is impaired by vecuronium during hypoxia.

BACKGROUND: Neuromuscular blocking agents reduce the human ventilatory response to hypoxia at partial neuromuscular block. It was hypothesized that vecuronium impairs carotid body chemoreceptor function during hypoxia. METHOD: The effect of systemic administration of vecuronium on single chemoreceptor activity during hypoxia, as recorded from a single nerve fiber preparation of the carotid sinus nerve, was studied in seven mechanically ventilated New Zealand White rabbits during continuous thiopental anesthesia. During normoventilation, the isocapnic hypoxic chemosensitivity of the single carotid body chemoreceptor was measured at four levels of oxygenation; these measurements were repeated at six separate occasions: control recording before injection, after intravenous administrations of 0.1 mg and 0.5 mg of vecuronium, and then at three occasions during a 90-min recovery period. Chemoreceptor chemosensitivity during isocapnic hypoxia was expressed as a hyperbolic function: Chemoreceptor output (Hz) = a + b x PaO2(-1) (mmHg). RESULTS: Chemosensitivity was reduced after both 0.1 mg and 0.5 mg vecuronium intravenous administration compared with control measurements; the hypoxic response curve was significantly depressed after both doses (P < 0.05). Notably, there was variation in the effect of vecuronium; some chemoreceptor preparations showed only minimal impairment, whereas some showed an almost abolished response to hypoxia. The chemosensitivity remained significantly depressed at 30 and 60 min but had recovered spontaneously at 90 min after 0.5 mg vecuronium. DISCUSSION: It is concluded that vecuronium depresses carotid body chemoreceptor function to a varying extent during hypoxia and that the depression recovers spontaneously.

Action Potentials↗

Function of the rat carotid body chemoreceptors in ageing.

Some age-related deficits in the ventilatory responses have been attributed to a decline in the functionality of the carotid body (CB) arterial chemoreceptors, but a systematic study of the CB function in ageing is lacking. In rats aged 3-24 months, we have performed quantitative morphometry on specific chemoreceptor tissue, assessed the function of chemoreceptor cells by measuring the content, synthesis and release of catecholamines (a chemoreceptor cell neurotransmitter) in normoxia and hypoxia, and determined the functional activity of the intact organ by measuring chemosensory activity in the carotid sinus nerve (CSN) in normoxia, hypoxia and hypercapnic acidosis. We found that with age CBs enlarge, but at the same time there is a concomitant decrease in the percentage of chemoreceptor tissue. CB content and turnover time for their catecholamines increase with age. Hypoxic stimulation of chemoreceptor cells elicits a smaller release of catecholamines in rats after 12 months of age, but a non-specific depolarizing stimulus elicits a comparable release at all ages. In parallel, there was a marked decrease in the responsiveness to hypoxia, but not to an acidic-hypercapnic stimulus, assessed as chemosensory activity in the CSN. We conclude that in aged mammals chemoreceptor cells become hypofunctional, leading to a decreased peripheral drive of ventilation.

Acidosis↗

Pharmacology of pH effects on carotid body chemoreceptors in vitro.

1. The carotid body and the carotid nerve were removed from anaesthetized cats and placed in a small Perspex channel through which Locke solution (at various pH values and usually equilibrated with 50% O(2) in N(2)) was allowed to flow. The glomus was immersed in the flowing solution while the nerve was lifted into oil covering the saline. Sensory discharges were recorded from the nerve and their frequency was used as an index of receptor activity. At times, a small segment of carotid artery, containing pressoreceptor endings, was removed together with the glomus. In this case, pressoreceptor discharges were recorded from the nerve.2. The amplitude of either chemo- or pressoreceptor discharges was not changed by strong acid solutions. Acid decreased the frequency of the baroreceptor discharges only when pH fell to less than 4.0. Solutions at low pH increased the chemosensory discharge, but acid depressed the increased chemoreceptor discharge elicited by KCl. These experiments indicated that H(+) ions probably acted as membrane ;stabilizers' without depolarizing either the nerve fibres or endings.3. Acid solutions increased the action of acetylcholine chloride (AChCl) (100-200 mug) on chemoreceptors. This effect probably was due either to inactivation of tissue cholinesterase or to enhanced sensitivity of the sensory endings to ACh.4. Choline chloride (10(-3)M), which favours ACh synthesis, protected the preparation against decay during prolonged experimentation. Hemicholinium-3 (HC-3), which blocks ACh synthesis in low concentrations (10(-5)M), depressed the chemosensory response to acid and to hypoxia when such stimuli were applied repeatedly. This concentration of HC-3 did not change effects of applied ACh.5. Substances which affect ACh release markedly changed the chemoreceptor discharge increase induced by acidity and other forms of stimulation. In the absence of Ca(2+), acid, anoxia, and interruption of flow provoked receptor depression while receptor excitation induced by ACh and KCl persisted. All stimuli excited and showed increased effectiveness as the Ca(2+) concentration was raised, but their effects declined as Ca(2+) was increased above normal values. Mg(2+) ions depressed the chemoreceptor effects induced by all these stimuli. The action of Mg(2+) was not due entirely to nerve ending block. Morphine sulphate (which decreases ACh release in other structures) also depressed the receptor response to acid and flow interruption.6. Cholinergic blocking agents such as mecamylamine, hexamethonium, atropine, dihydro-beta-erithroidine (DHE), HC-3 (10(-4)M), choline and acetylcholine (in combination with choline) depressed the effects of acid and ACh on the chemoreceptors. The effect induced by interruption of flow was depressed only by mecamylamine and DHE.7. Agents which affect the fate of released ACh, such as acetylcholinesterase and eserine salicylate, did not affect clearly the response of chemoreceptors to acid.8. The results suggest that acid stimulates chemoreceptor fibres through an indirect mechanism, viz. through increased release and/or decreased destruction of a presynaptic transmitter from the glomus cell. This transmitter is probably ACh (see following paper, Eyzaguirre & Zapata, 1968).

Acetylcholine↗

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↗

The interaction of reflexes elicited by stimulation of carotid body chemoreceptors and receptors in the nasal mucosa affecting respiration and pulse interval in the dog.

1. The effects on respiration and pulse interval of stimulation of the carotid body chemoreceptors before, during and after stimulation of receptors in the nose have been studied in the anaesthetized dog.2. Stimulation of a carotid body by infusion of cyanide into the ipsi-lateral common carotid artery causes hyperpnoea and either an increase, decrease or no change in pulse interval.3. Excitation of receptors in the nasal mucosa leads to reflex apnoea or a reduction in breathing, and an increase in pulse interval.4. When the carotid bodies are excited by the same dose of cyanide during stimulation of the nasal mucosa, the chemoreceptor-respiratory response is abolished or reduced in size compared with the control effect. On the other hand, the chemoreceptor-cardio-inhibitory response is considerably enhanced.5. The potentiated cardio-inhibitory response of combined chemoreceptor and nasal stimulation could not be accounted for by the change in pulmonary ventilation, arterial P(O2) or P(CO2), or mean arterial blood pressure.6. These results indicate that excitation of the nasal reflex inhibits the chemoreceptor-respiratory reflex response but facilitates the chemoreceptor-cardio-inhibitory reflex response. The possible sites of these interactions between the nasal and chemoreceptor reflexes are discussed.

Animals↗

Baroreceptor and chemoreceptor influences on heart rate during the respiratory cycle in the dog.

1. Brief stimuli were delivered to the carotid chemoreceptors or baroreceptors in dogs anaesthetized with pentobarbitone or chloralose. Chemoreceptor stimulation was achieved by rapid retrograde injections of 0-2-0-5 ml. warmed, CO2-equilibrated saline through a cannula in the external carotid artery. Baroreceptor stimulation was achieved by forceful retrograde injection of 2-5 ml. air-equilibrated saline, or of freshly drawn arterial blood, into the external carotid artery after first clamping the common carotid artery. 2. Brief baroreceptor stimuli had no noticeable effect on breathing. Brief chemoreceptor stimuli had no effect on breathing in some dogs, but in many produced a reflex increase in the depth of inspiration when delivered during inspiration. In these same dogs, brief chemoreceptor stimuli delivered in expiration either prolonged the expiratory pause or evoked an active expiratory effort. 3. Prompt decreases in heart rate were elicited by brief sudden chemoreceptor or baroreceptor stimuli when these were delivered during the expiratory phase of respiration. The stimuli did not modify the control heart rate pattern when delivered during inspiration. If the carotid sinus nerve or the vagus nerves were cut the responses were abolished. 4. Brief chemoreceptor or baroreceptor stimuli remained effective in evoking prompt decreases in heart rate during periods of apnoea in the end-inspiratory position (Hering-Breuer inflation reflex). In periods of apnoea after prolonged artificial hyperventilation the stimuli were sometimes ineffective at first, but were always effective late in the period of apnoea, again producing prompt cardiac slowing. 5. After denervation of the lungs, brief baroreceptor and chemoreceptor stimuli continued to evoke prompt falls in heart rate when given during expiration. When delivered during inspiration the same stimuli were either ineffective, or less effective.

Anesthesia, General↗

The response to hypoxia of arterial chemoreceptors in fetal sheep and new-born lambs.

Carotid chemoreceptor activity was detected in each of fourteen halothane or pentobarbitone anaesthetized exteriorized fetal lambs of 90-143 days gestational age. Activity was about 5 Hz at a Pa,O2 of 25 mmHg and it increased as Pa,O2 was reduced, either by compressing the umbilical cord or by reducing the (FIO2) oxygen fraction of the gas used to ventilate the ewe. Activity increased briskly when 1-2 ml CO2-saturated saline was injected retrogradely into the lingual artery, but not when saline of pH 7.4 or fetal arterial blood was injected. In two fetuses near-term chemoreceptor activity was recorded continuously whilst the umbilical cord was ligated and ventilation with air started. Activity increased 200-500% as Pa,O2 fell, but then fell to below control as Pa,O2 rose. We suggest that these changes in activity reflect those occurring naturally at birth. No spontaneous chemoreceptor activity could be detected on the day of birth in twelve pentobarbitone anaesthetized lambs delivered vaginally or by Caesarean section at 135-146 days. Single baroreceptor activity could however be recorded in these lambs, and chemoreceptor activity could be elicited by hypercapnia. Spontaneous chemoreceptor activity was detected in six of seven lambs more than 2 days old. In eight conscious lambs the steady-state respiratory response to isocapnic hypoxia was variable on the day of birth. In six of these lambs the response was significantly greater by the third day. We conclude that the arterial chemoreceptors are active and responsive in the fetus, but quiescent in the lamb on the day of birth when Pa,O2 has risen. The hypoxic sensitivity of the chemoreceptors is reset from the fetal to the adult range over the next few days.

Action Potentials↗

Effect of cephalic carbon dioxide tension on the cardiac inotropic response to carotid chemoreceptor stimulation in dogs.

Dogs were anaesthetized with chloralose and the cephalic circulation was perfused, through the brachiocephalic and left subclavian arteries, with blood equilibrated with various tensions of CO2. The vascularly isolated carotid bifurcations were perfused at a constant pressure with either arterial or venous blood. Inotropic responses were assessed by measuring the maximum rate of change of left ventricular pressure (dP/dt max) with heart rate and aortic pressure held constant. Stimulation of carotid chemoreceptors with venous blood, at all values of cephalic PCO2, always resulted in a decrease in dP/dt max. An increase in cephalic PCO2, during arterial perfusion of chemoreceptors, resulted in an increase in dP/dt max and the response to chemoreceptor stimulation was enhanced. Graded changes in cephalic PCO2 resulted in graded changes in dP/dt max during arterial perfusion of chemoreceptors. However, the value of dP/dt max during venous perfusion was not significantly affected by increases in cephalic PCO2 above normal but it did decrease significantly during cephalic hypocapnia. These results confirm that an increase in cephalic PCO2 and stimulation of carotid chemoreceptors result in opposite responses of the cardiac inotropic state. The responses to chemoreceptor stimulation were enhanced by cephalic hypercapnia but the responses to cephalic hypercapnia, although not to hypocapnia, were suppressed by chemoreceptor stimulation.

Animals↗

The effect of small changes in arterial carbon dioxide tension on carotid chemoreceptor activity in the cat.

The hypothesis that the fluctuations in carotid chemoreceptor discharge represent more than a simple proportional response to respiratory oscillations of Pa, CO2 has been examined. Simultaneous recordings of the activity in few- or multi-fibre chemoreceptor preparations of the cut carotid sinus nerve and oscillations of carotid arterial pH have been made in four anaesthetized cats which were paralysed and artificially ventilated at constant frequency. Chemoreceptor activity was averaged over a minimum of twenty consecutive pH cycles and the amplitude of the fluctuations in discharge frequency determined. Using the mean Pa, CO2 obtained from blood-gas analysis and the slope of the relationship between log Pa, CO2 and pH obtained in each cat, the amplitude of the pH oscillations was converted to Pa, CO2 amplitude. This amplitude relative to the mean Pa, CO2 has been compared with the amplitude of the corresponding fluctuation in the chemoreceptor discharge frequency recorded from the carotid sinus nerve (e.s.n.d. amplitude) relative to its mean level. Whereas the Pa, CO2 amplitude was always less than 8% of the mean Pa, CO2, the c.s.n.d. amplitude ranged from 40 to 186% of the mean discharge frequency. C.s.n.d. amplitude was divided by the corresponding Pa, CO2 amplitude to give an index of the sensitivity of the chemoreceptors to Pa, CO2. This sensitivity has been compared with that determined from the mean discharge frequency produced in response to changes in mean Pa, CO2 comparable in magnitude to the Pa, CO2 amplitude. The former sensitivity was usually at least 3 times greater than the latter. Examination of the fluctuations in chemoreceptor discharge frequency in relation to the corresponding pH oscillations revealed that whereas the minimum discharge frequency coincided with the alkaline peak of the pH oscillation (trough of the Pa, CO2 oscillation), the maximum discharge frequency did not invariably coincide with the acid trough of the pH oscillation (peak of the Pa, CO2 oscillation). On 30% of occasions, the maximum discharge frequency was associated with the region of maximum rate of fall of pH (maximum rate of rise of Pa, CO2). It was concluded that fluctuations in the discharge of carotid chemoreceptors cannot be accounted for on the basis of a simple proportional relationship to Pa, CO2. They contain a large rate of change component.

Action Potentials↗

The influence of the sympathetic outflow on aortic chemoreceptors of the cat during hypoxia and hypercapnia.

1. An attempt has been made to reconcile differing observations, made by different groups of investigators, on the responses of aortic chemoreceptors of cats during normoxia, hypoxia and hypercapnia. 2. In cats anaesthetized with sodium pentobarbitone it was observed that during hypoxic stimulation of twelve chemoreceptors, an intravenous injection of about 20 mg sodium pentobarbitone produced hypotension which was accompanied by an initial fall in chemoreceptor activity instead of the expected increase that invariably occurred in all the receptors when hypotension was produced mechanically by distending a balloon in the right atrium (twenty-six during normoxia, eleven during hypoxia and eight during hypercapnia). 3. In twelve receptors a reflex fall in blood pressure produced by injecting 8-25 micrograms veratridine (Bezold-Jarisch reflex) yielded results qualitatively similar to those following injection of sodium pentobarbitone. 4. In sixteen out of twenty-five chemoreceptors it was observed that ventilating the cat with 5.6-6.7% CO2 produced either no or little increase in activity; in nine receptors there was a clear increase in activity, which fell initially or was abolished after injecting a single dose of 20 mg sodium pentobarbitone. 5. In all seven chemoreceptors tested in seven deeply anaesthetized cats it was found that a larger dose (about 50-60 mg) of sodium pentobarbitone had no direct depressant effect on aortic chemoreceptor activity. It followed that the initial depressant effect of the much smaller doses of sodium pentobarbitone observed during hypoxic and hypercapnic stimulation (see above) must be due to reduction in the sympathetic outflow to the aortic bodies. This conclusion was supported by the results following injections of veratridine. 6. By comparing the present results with those reported previously it was concluded that the variations in the responses of aortic chemoreceptors during hypoxia and hypercapnia reported by different investigators could be partly due to variations in the level of sympathetic activity prevailing under different experimental conditions.

Action Potentials↗

Release of dopamine and chemoreceptor discharge induced by low pH and high PCO2 stimulation of the cat carotid body.

1. Cat carotid bodies were incubated with the precursor [3H]tyrosine to label the catecholamine deposits and then mounted in a superfusion chamber which allowed simultaneous collection of the released [3H]dopamine (DA) and recording of action potentials from the carotid sinus nerve. 2. Low pH (7.2-6.6) superfusion of the carotid bodies for periods of 10 min produced a parallel increase in the release of [3H]DA and chemoreceptor discharge. 3. Carotid sinus nerve denervation of the carotid body 12-15 days prior to the experiments did not modify the release of [3H]DA elicited by low pH. 4. Superfusion of the carotid bodies with Ca(2+)-free, high-Mg2+ (1.6 mM) media reduced basal release of [3H]DA and chemoreceptor discharge by about 30%. Release evoked by low pH was reduced by 82%. Peak and average chemoreceptor discharge recorded in response to low pH were reduced by 28%. 5. Solutions containing weak acids (sodium acetate, 10 mM), adjusted at pH 7.4, elicited release of [3H]DA and increased chemoreceptor discharge. 6. With HCO3-CO2-buffered superfusion media, a reduction of bicarbonate to 5.6 mM (pH 6.8), an increase in CO2 to 20% (pH 6.8), or a simultaneous increase in CO2 to 20% and bicarbonate to 90 mM (pH 7.4), resulted in all cases in a corresponding increase in [3H]DA release and chemoreceptor discharge. The most effective stimulus was 20% CO2-pH 6.8 and the least effective 5% CO2-5.6 mM-HCO3-pH 6.8. 7. Inhibition of carbonic anhydrase with acetazolamide while perfusing the carotid bodies with a 20% CO2-equilibrated (pH 7.4) solution resulted in comparable reductions in the release of [3H]DA and chemoreceptor discharge. 8. It is concluded that the effective acidic stimulus at the carotid body chemoreceptors is an increase in hydrogen ion concentration in type I cells. It is also concluded that DA plays a critical role in the genesis of carotid sinus nerve discharges.

Acetazolamide↗

Maturation of carotid chemoreceptor sensitivity to hypoxia: in vitro studies in the newborn rat.

1. A preparation was developed to record single-fibre chemoreceptor afferent activity from carotid bodies of newborn and adult rats in vitro. The response to severe hypoxia was studied as a function of developmental age in four age groups: 1-2, 4-7, 10-15 days and adult (25-30 days). 2. During superfusion with HEPES-saline at room PO2 and at 26 or 35 degrees C, afferent chemoreceptor activity could be recorded in all age groups. No significant difference was found among groups in baseline discharge frequency at 26 or 35 degrees C. 3. All chemoreceptors responded to anoxia (PO2 congruent to 0 Torr) with a rapid increase in discharge frequency. At 35 degrees C, peak discharge frequency of single chemoreceptor afferents was significantly greater in the adult (15.7 +/- 1.6 Hz, mean +/- S.E.M., n = 18) and 10-15 days (11.2 +/- 4.2, n = 8) compared to rats of 1-2 days (4.3 +/- 0.7, n = 14) and 4-7 days of age (3.9 +/- 1.0, n = 7). 4. At 2 min into the anoxia period, all chemoreceptor activities were reduced from their peak discharge levels. At 35 degrees C, this decrease was significantly greater in the adult compared to the newborn. 5. During the period of decreased activity during anoxia, the chemoreceptor discharge could not be increased by inter-stream injection of acetylcholine (100 micrograms) or dopamine (100 micrograms), although these drugs were effective in increasing discharge rate prior to hypoxia. 6. We conclude that: (1) postnatal maturation of chemoreceptor sensitivity to hypoxia is present in vitro, (2) maturation occurs between the first and second week after birth in the rat, and (3) the decrease in activity during prolonged anoxia is not greater in the newborn compared to the adult. Thus, maturational changes occur in the sensitivity of the glomus cell-nerve ending complex to hypoxia.

Aging↗

Sensory afferent selective role of P2 receptors in the nucleus tractus solitarii for mediating the cardiac component of the peripheral chemoreceptor reflex in rats.

We have assessed the functional role of type 2 purinergic (P2) receptors within the caudal aspect of the commissural nucleus tractus solitarii (NTS) in mediating the peripheral chemoreceptor reflex cardiorespiratory response in the arterially perfused in situ working heart-brainstem preparation of rats. Microinjection in NTS of either suramin (100 pmol) or pyrinoxalphosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium salt (PPADS; 10 pmol) depressed the reflex bradycardia (by approximately 50 %), but not the tachypnoea, following peripheral chemoreceptor stimulation. In contrast, the reflex bradycardia produced by stimulation of pharyngo-oesophageal receptors was unaffected. Furthermore, microinjections in NTS of the P2X receptor agonist alpha,beta-methyleneadenosine 5'-triphosphate (10 pmol) evoked a bradycardia which was antagonized by suramin (100 pmol). This P2X agonist reversibly potentiated the peripheral chemoreceptor-evoked bradycardia. The effect of suramin was selective to purinergic receptors because the bradycardia evoked by microinjection of alpha,beta-methyleneadenosine 5'-triphosphate was blocked while the bradycardic responses to microinjections of NMDA or non-NMDA receptor agonists were not affected. From whole-cell recordings, some NTS neurones received convergent excitatory synaptic inputs from both peripheral chemoreceptors and receptors at the pharyngo-oesophageal junction. The excitatory postsynaptic response evoked by chemoreceptor stimulation was depressed by suramin, but convergent excitatory inputs from pharyngo-oesophageal receptors were unperturbed. Our findings support the hypothesis that caudal commissural NTS P2 purinergic receptors play a role in the neurotransmission of the parasympathetic (bradycardic) component of the chemoreceptor reflex. This effect is highly selective in that the chemoreceptor afferent-evoked tachypnoea, as well as other visceral receptor-mediated reflex bradycardia, remain unaffected.

Action Potentials↗

Relative latency of responses of chemoreceptor afferents from aortic and carotid bodies.

Discharges from aortic and carotid body chemoreceptor afferents were simultaneously recorded in 18 anesthetized cats to test the hypothesis that aortic chemoreceptors, because of their proximity to the heart, respond to changes in arterial blood gases before carotid chemoreceptors. We found that carotid chemoreceptor responses to the onset of hypoxia and hypercapnia, and to the intravenously administered excitatory drugs (cyanide, nicotine, and doxapram), preceded those of aortic chemoreceptors. Postulating that this unexpected result was due to differences in microcirculation and mass transport, we also investigated their relative speed of responses to changes in arterial blood pressure. The aortic chemoreceptors responded to decreases in arterial blood pressure before the carotid chemoreceptors, supporting the idea that the aortic body has microcirculatory impediments not generally present in the carotid body. These findings strengthened the concept that carotid bodies are more suited for monitoring blood gas changes due to respiration, whereas aortic bodies are for monitoring circulation.

Action Potentials↗

Differential effects of oligomycin on carotid chemoreceptor responses to O2 and CO2 in the cat.

Effects of oligomycin on carotid chemoreceptor responses to O2 and CO2 were investigated using an in situ perfusion technique. Cats were anesthetized, paralyzed, and artificially ventilated. To avoid a possible reaction between an oligomycin-ethanol mixture and blood, we administered oligomycin to the carotid body via cell- and protein-free perfusate. Except for the perfusion periods, the carotid body received its own natural blood supply. Responses to O2, CO2, sodium cyanide, and nicotine of the same carotid chemoreceptor afferents were studied before and after each perfusion. An appropriate low dose of oligomycin completely blocked carotid chemoreceptor response to O2 while preserving the CO2 response. At the same time cyanide response was attenuated leaving nicotine response intact. Additional doses of oligomycin attenuated carotid chemoreceptor response to CO2 as well. Perfusion with a blank solution containing ethanol did not change the carotid body chemoreceptor responses. These effects of oligomycin on carotid chemoreceptor responses to O2 and CO2 were reversible, and restoration of the response to CO2 preceded that to O2. In addition, oligomycin administered into the blood with close intra-arterial injection produced similar differential blockade of O2 and CO2 chemoreception, preserving the nicotine and dopamine effects. This study confirmed the previous findings and provided new evidence showing that 1) the responses of carotid chemoreceptor to O2 and CO2 were separable by oligomycin due to the inhibition of oxidative phosphorylation and 2) the responses to nicotine and dopamine were intact even after blockade of O2 response.

Animals↗

Vagal and chemoreceptor influences on abdominal muscle activity in awake lambs during hypoxia.

The ventilatory response to hypoxia is a complex phenomenon involving several control mechanisms. We designed this study to examine the dynamic control of abdominal muscle expiratory electromyogram (EMG) activity during room-air breathing and hypoxia and then to analyze the relative contribution of the chemoreceptors and vagal afferents. We studied 12 11- to 22-day-old awake nonsedated lambs, six intact and six vagotomized. To assess the dynamic influence of peripheral chemoreceptors on abdominal muscle expiratory activity, we performed transient testing of peripheral chemoreceptor function (pure O2 and N2 inhalation, KCN injection). To assess the influence of central chemoreceptor afferents, we compared results obtained during hypocapnic and isocapnic 15-min hypoxic runs (fractional concentration of inspired O2 0.08) in each lamb. We also compared results obtained in intact and vagotomized lambs so that the importance of vagal afferents could be assessed. We consistently observed abdominal muscle expiratory EMG activity in each lamb, whether intact or vagotomized, during baseline room air breathing; further recruitment was observed during hypoxia. We also consistently observed abdominal muscle expiratory recruitment during hypocapnic hypoxia in each lamb, although it was significantly less marked than during isocapnic hypoxia. Our transient testing of peripheral chemoreceptor function showed, furthermore, that peripheral chemoreceptor afferents dynamically modulate abdominal muscle expiratory activity. Thus, during hypoxia in 11- to 22-day-old awake nonsedated lambs, increased afferent information from peripheral chemoreceptors forcefully enhances abdominal muscle expiratory activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗