Chemoreceptor Afferent Fibers Research Articles

Carotid chemoreceptor afferent projections to leptin receptor containing neurons in nucleus of the solitary tract

Neurons expressing the leptin receptor (Ob-R) exist within the caudal nucleus of the solitary tract (NTS). Additionally, afferent neurons expressing the Ob-R have been identified within the nodose ganglion and NTS. Furthermore, systemic injections or focal injections of leptin directly into NTS potentiate the response of NTS neurons to carotid chemoreceptor activation. However, the distribution of carotid body afferents in relation to Ob-R containing neurons within NTS is not known. In this study, chemoreceptor afferent fibers were labeled following microinjection of the anterograde tract tracer biotinylated dextran amine (BDA) into the carotid body or petrosal/nodose ganglion of Wistar rats. After a survival period of 10–14 days, the NTS was processed for BDA and Ob-R immunoreactivity. Afferent axons originating in the carotid body were found to project to the lateral (Slt), gelantinosa (Sg), and medial (Sm) subnuclei of the NTS complex. A similar, but more robust distribution of BDA labeled fibers was observed in the NTS complex after injections into the petrosal/nodose ganglion. Carotid body BDA labeled fibers were observed in close apposition to Ob-R immunoreactive neurons in the region of Slt, Sg and Sm. In addition, a small number of carotid body afferents were found to contain both BDA and express Ob-R-like immunoreactivity within the regions of Slt, Sg and Sm. Taken together, these data suggest that leptin may modulate carotid chemoreceptor function not only through direct effects on NTS neurons, but also through a direct effect on carotid body primary afferent fibers that innervate NTS neurons.

Perinatal hyperoxia for 14 days increases nerve conduction time and the acute unitary response to hypoxia of rat carotid body chemoreceptors

Hyperoxia in the immediate perinatal period, but not in adult life, is associated with a life-long impairment of the ventilatory response to acute hypoxia. This effect is attributed to a functional impairment of peripheral chemoreceptors, including a reduction in the number of chemoreceptor afferent fibers and a reduction in "whole nerve" afferent activity. The purpose of the present study was to assess the activity levels of single chemoreceptor units in the immediate posthyperoxic period to determine whether functional impairment extended to single chemoreceptor units and whether the impairment was only induced by hyperoxia exposure in the immediate postnatal period. Two groups of rat pups were exposed to 60% inspired O2 fraction for 2 wk at ages 0-14 days and 14-28 days, at which time single-unit activities were isolated and recorded in vitro. Compared with control pups, hyperoxia-treated pups had a 10-fold reduction in baseline (normoxia) spiking activity. Peak unit responses to 12, 5, and 0% O2 were reduced and nerve conduction time was significantly slower in both hyperoxia-treated groups compared with control groups. We conclude that 1) hyperoxia greatly reduces single-unit chemoreceptor activities during normoxia and acute hypoxia, 2) the treatment effect is not limited to the immediate newborn period, and 3) at least part of the impairment may be due to changes in the afferent axonal excitability.

Dopamine modulates synaptic transmission in the nucleus of the solitary tract.

10.1152/jn.00224.2002. Dopamine (DA) modulates the cardiorespiratory reflex by peripheral and central mechanisms. The aim of this study was to examine the role of DA in synaptic transmission of the nucleus tractus solitarius (NTS), the major integration site for cardiopulmonary reflexes. To examine DA's role, we used whole cell, voltage-clamp recordings in a rat horizontal brain stem slice. Solitary tract stimulation evoked excitatory postsynaptic currents (EPSCs) that were reduced to 70 +/- 5% of control by DA (100 microM). The reduction in EPSCs by DA was accompanied by a decrease in the paired pulse depression ratio with little or no change in input resistance or EPSC decay, suggesting a presynaptic mechanism. The D1-like agonist SKF 38393 Br (30 microM) did not alter EPSC amplitude, whereas the D2-like agonist, quinpirole HCl (30 microM), depressed EPSCs to 73 +/- 4% of control. The D2-like receptor antagonist, sulpiride (20 microM), abolished DA modulation of EPSCs. Most importantly, sulpiride alone increased EPSCs to 131 +/- 10% of control, suggesting a tonic D2-like modulation of synaptic transmission in the NTS. Examination of spontaneous EPSCs revealed DA reversibly decreased the frequency of events from 9.4 +/- 2.2 to 6.2 +/- 1.4 Hz. Sulpiride, however, did not alter spontaneous events. Immunohistochemistry of NTS slices demonstrated that D2 receptors colocalized with synaptophysin and substance P, confirming a presynaptic distribution. D2 receptors also localized to cultured petrosal neurons, the soma of presynaptic afferent fibers. In the petrosal neurons, D2 was found in cells that were TH-immunopositive, suggesting they were chemoreceptor afferent fibers. These results demonstrate that DA tonically modulates synaptic activity between afferent sensory fibers and secondary relay neurons in the NTS via a presynaptic D2-like mechanism.

Electrical properties of chemoreceptor elements in the carotid body.

The electrical properties of chemoreceptor afferent nerve fibers and glomus cells and the behavior of cytosolic Ca(2+) in glomus cells are reviewed. While this has not been confirmed, spontaneously depolarizing potentials (SDPs) recorded in a chemoreceptor afferent terminal may be the postsynaptic expression of presynaptic events. Glomus cells, which are presynaptic elements, either depolarized or hyperpolarized in response to natural and chemical stimulation. After-hyperpolarization following an initial depolarization and after-depolarization following an initial hyperpolarization were often seen. When a glomus cell depolarizes, voltage noise increases despite a decrease in input resistance in both intact and denervated carotid bodies. The voltage noise may be "receptor noise" generated in the glomus cell itself. The electrical properties of glomus cells change in the denervated carotid body, which suggests that the chemoreceptor afferent nerve exerts some trophic effect(s) on glomus cells. Hypoxia either increases or decreases cytosolic Ca(2+), while ACh or NaCN induces either an increase or no change in cytosolic Ca(2+) in glomus cells. There are at least two possible explanations for voltage changes in glomus cells: a chemical stimulus first depolarizes the glomus cell and induces Ca(2+) influx to release chemical substances, or a chemical stimulus induces an increase in [Ca(2+)](i) and then hyperpolarizes the glomus cell via potassium influx.

Chemosensory activity from single or few-fibres of the carotid sinus nerve in the guinea-pig

Humans who are born and raised at high altitude possess a blunted breathing response to hypoxia. The guinea-pig also has a blunted breathing response to hypoxia [1], which may be linked to its high altitude origin in South America. Our laboratory has shown that the carotid bodies of the guinea-pig are not required for the breathing response to hypoxia [1]. Whether the carotid bodies can actually detect hypoxia is uncertain because the central depressive effects associated with hypoxia may attenuate the breathing response to an otherwise potent carotid body stimulant. In a recent study, we looked for evidence of chemoreceptor activity in the whole carotid sinus nerve (CSN), but found that the whole CSN activity was dominated by baroreceptor afferent activity [2]. In this study activity was recorded from single or few-fibre CSN filaments during application of the chemoreceptor stimulants NaCN (200 μgkg-1 i.v.), 8% CO2 (60 s) and 8% O2 (60 s), from guinea-pigs (n = 10; ~420 g; ~50 days old) that were anaesthetised with ketamine/xylazine (20/1 mgkg-1). Of the 10 guinea-pigs, only 8 fibre preparations containing chemoreceptor activity were successfully obtained from 4 guinea-pigs. In general, most of the isolated nerve filaments were multi-fibre preparations. Basal chemoreceptor activity could not be detected. However, NaCN and hypercapnia increased activity in 5 of the fibre preparations that were otherwise silent, or that contained 1 or 2 baroreceptor fibres. The magnitude of response varied considerably between filaments because of the different number of individual fibres in each preparation and, thus, the difference in the actual count of action potentials. Only one of the fibre preparations responded to hypoxia with an increase in activity; no fibres responded with a decrease in activity. The physiological relevance of the latter results could be similar to that of the aortic depressor nerve (ADN) in the rat. Brophy et al. revealed that, in contrast to the general consensus, the rat ADN does contain chemoreceptor afferent fibres, and that such fibres are stimulated by chemoreceptor stimulants [3]. Kobayashi et al. agreed that chemoreceptor fibres were present, but concluded that the rat ADN does not contain a functionally significant number of chemoreceptor afferent fibres that could appreciably contribute to the generation of chemoreflexes [4]. The present study has shown that the carotid bodies of the guinea-pig can detect NaCN and hypercapnia, as expected, and also hypoxia, although the latter was a comparatively weak stimulant. In conclusion, the physiological relevance of the carotid body of the guinea-pig for the ventilatory responses to hypoxia remains uncertain.

Stimulus-specific signaling pathways in rabbit carotid body chemoreceptors

The carotid body is an arterial chemosensory organ which responds to multiple natural and pharmacological stimuli, including hypoxia and nicotine. Numerous studies have investigated the initial molecular events which activate chemosensory type I cells in the carotid body, but less attention has been focused on later steps in the transduction cascade, which mediate neurotransmitter release from type I cells and excitation of chemoreceptor afferent fibers in the carotid sinus nerve. In the present study, we examined the effects of a highly specific inhibitor of calcium/calmodulin-dependent kinase II, KN-62, and a calmodulin inhibitor, trifluoperazine, on carotid sinus nerve activity and catecholamine release evoked from rabbit carotid bodies superfused in vitro. KN-62 did not alter sinus nerve activity and catecholamine release evoked by hypoxia, but this agent significantly reduced nerve activity and neurotransmitter release evoked by 100 μM nicotine. Trifluoperazine (10 μM), likewise inhibited activity evoked by nicotine, as well as hypoxia. Basal levels of nerve activity and catecholamine release (established in superfusate equilibrated with 100% O 2) were unaffected by all drug treatments. Separate biochemical experiments showed that Ca 2+/calmodulin-dependent incorporation of 32P into carotid body particulate proteins is significantly reduced following incubation of intact carotid bodies in nicotine, but not following exposure to hypoxia. Our observations suggest that excitation of the carotid body by diverse stimuli may involve the activation of distinct, stimulus-specific transduction pathways. Furthermore, these data correlate with our previous findings which showed that hypoxia, on the one hand, and nicotine on the other, evoke the preferential release of either dopamine or norepinephrine, respectively, from carotid bodies incubated in vitro.

Is the aortic depressor nerve involved in arterial chemoreflexes in rats?

Recent anatomical and physiological studies showed that chemoreceptor afferent fibers are present in the rat aortic depressor nerve (ADN), which has been considered to contain exclusively baroreceptor afferent fibers. However, it remains to be proven whether the chemoreceptor afferents of the ADN are practically involved in chemoreflexes. The present study was performed in chloralose/urethane-anesthetized rats of either Sprague–Dawley (SD) or Wistar strain to examine whether the ADN carries sufficient information regarding arterial hypoxia and hypercapnia, and whether the ADN indeed participates in chemoreflexes, the circulatory and respiratory components. It was found in either strain that afferent discharges of the ADN were not affected at all by hypoxia or hypercapnia, whereas those of the carotid sinus nerve (CSN) markedly increased due to these stimuli. Hypoxia produced hypertension, transient bradycardia followed by tachycardia, and respiratory facilitation, which characterize the chemoreflexes. Any of these responses was not affected at all by the ADN section, but all were abolished by the CSN section. Intraaortic injection of cyanide also induced transient bradycardia and respiratory facilitation, but any of them was not affected by the ADN section while all were abolished by the CSN section. Furthermore, electrical stimulation of the ADN produced solely baroreflex responses, i.e. hypotension and respiratory suppression, whereas that of the CSN provoked chemoreflex responses, i.e. early, transient hypertension and respiratory facilitation. In conclusion, the rat ADN does not contain a functionally significant number of chemoreceptor afferent fibers, if at all, and does not appreciably contribute to generation of chemoreflexes.

Hereditarily elongated carotid sinus nerve in a rat colony

A specific colony of Wistar rats was found in which the common carotid artery bifurcates at an unusually caudal position, thereby the carotid sinus nerve that originates from the bifurcation is elongated. The present study was done to determine whether this elongated nerve carries baro- and chemosensations in the same manner as the carotid sinus nerve of conventional rats or of other species. In chloralose-urethane anesthetized rats of this specific colony, the afferent discharges were recorded from the elongated carotid sinus nerve in response to a phenylephrine-induced rise in blood pressure and a fall in oxygen tension, as well as an increase in carbon dioxide tension in the respiratory gas. Reflex effects of electrical stimulation of the nerve were also examined. In nerve recording, the afferent discharges of the elongated carotid sinus nerve were increased by any of the perturbations, hypertensive, hypoxic or hypercapnic. Electrical stimulation of the elongated carotid sinus nerve caused an initial rise and a subsequent fall in blood pressure, bradycardia, and an increase of respiratory volume and rate. These results confirmed that the elongated carotid sinus nerve of rats in this colony contains both baroreceptor and chemoreceptor afferent fibers. It seems that this colony of rats proffers a beneficial material which will facilitate the studies to analyze the features and reflex functions of carotid body chemoreceptors and/or carotid sinus baroreceptors.

Excitatory amino acid receptors within NTS mediate arterial chemoreceptor reflexes in rats.

The nucleus tractus solitarius (NTS) is the primary site of termination of arterial baroreceptor and chemoreceptor afferent fibers. Excitatory amino acid (EAA) receptors within NTS have been shown to play an important role in the mediation of arterial baroreceptor reflexes; however, the importance of EAA receptors within NTS in the mediation of arterial chemoreceptor reflexes remains controversial. Therefore, in chloralose-urethan-anesthetized, mechanically ventilated, paralyzed rats, 4 nmol of the broad-spectrum EAA receptor antagonist kynurenic acid (Kyn) was injected into the NTS to observe the effects of EAA receptor blockade on the pressor responses evoked by either activation of ipsilateral carotid body chemoreceptors (by close arterial injection of CO2-saturated bicarbonate) or electrical stimulation of ipsilateral carotid sinus nerve (CSN). Under control conditions, activation of carotid body chemoreceptors and CSN stimulation evoked increases in arterial pressure of 27 +/- 2 (n = 24 sites) and 28 +/- 3% (n = 8), respectively. Kyn microinjection into NTS significantly reduced the pressor responses evoked by activation of carotid body chemoreceptors and electrical stimulation of the CSN for 20 and 25 min, respectively. Attenuation of pressor responses evoked by chemoreceptor activation were maximal at 20 min post-Kyn injection (13 +/- 2%), whereas CSN-evoked pressor responses were maximally attenuated at 15 min (6 +/- 4%). Microinjection into NTS of 4 nmol of xanthurenic acid, a structural analogue of Kyn with no EAA receptor antagonist properties, had no effect on chemoreceptor reflexes. We conclude that EAA receptors within NTS play an important role in the mediation of arterial chemoreceptor reflexes.

Carotid chemoreceptor function and structure in the atherosclerotic rabbit: respiratory and cardiovascular responses to hyperoxia, hypoxia and hypercapnia.

We tested the following hypothesis: if carotid body blood flow, and hence the relationship of the frequency of discharge in chemoreceptor afferent fibres to arterial PO2, were affected by atherosclerotic change, then a modification of the control of the respiratory and cardiovascular systems might result. Carotid body reflexes were therefore studied in conscious atherosclerotic rabbits and a control group of normal animals breathing 100% O2, three hypoxic gas mixtures to which was added sufficient CO2 to maintain the arterial PCO2 constant, and 2% and 4% CO2 in 21% O2 and N2. When breathing room air, the atherosclerotic rabbits breathed at a higher respiratory frequency and lower tidal volume than the normal animals, although there was no difference in the respiratory minute volume. The respiratory and cardiovascular responses to hyperoxia, isocapnic hypoxia and hypercapnia were essentially the same in both groups of animals. Serial sections of the carotid bodies showed pathological changes including interstitial fibrosis in the caudal part with interstitial haemorrhages. The proximal part of the ascending pharyngeal artery, the vessel supplying the organ, and its origin from the external carotid, and the arterioles in the caudal part of the carotid body were nearly always occluded to a varying extent by atheromatous plaques. The capillaries appeared normal under light microscopy. The rostral-caudal lengths of the carotid bodies were similar in the two groups. We conclude that the peripheral arterial chemoreceptor responses in atherosclerotic rabbits are relatively normal even though the arteries to, and arterioles within, the carotid body are partly occluded.

Ventrolateral medullary neurons relay cardiovascular inputs to the paraventricular nucleus.

Horseradish peroxidase (HRP) and single-unit recording experiments were done in cats to identify neurons in ventrolateral medulla (VLM) that project directly to the paraventricular nucleus (PVH) and relay cardiovascular information from carotid sinus (CSN) and aortic depressor (ADN) nerves. After diffusion of HRP into the PVH, retrogradely labeled neurons were observed in the VLM. The region of the VLM containing HRP-labeled neurons was then explored for single units antidromically activated by stimulation of the PVH in chloralosed, paralyzed, and artificially ventilated cats. These units were then tested for their responses to stimulation of the CSN and ADN. Antidromic potentials were recorded from 100 units in the VLM. Of these units, 65% were orthodromically excited by stimulation of buffer nerves; 28 by only CSN, 19 by only ADN, and 18 by both CSN and ADN. The axons of antidromically activated units responding to buffer nerves conducted at slower velocities than those of nonresponsive units. These data demonstrate that VLM neurons projecting directly to PVH integrate cardiovascular afferent information and suggest that these VLM neurons may be involved in the control of the activity of magnocellular neurosecretory neurons in the PVH during activation of baroreceptor and chemoreceptor afferent fibers.

The central projections of carotid baroreceptors and chemoreceptors in the cat: a neurophysiological study.

The medullary projections of afferent neurons with cell bodies in the petrosal ganglion have been investigated using an antidromic mapping technique. Of the ninety-three units studied, fifty-eight were shown to have patterns of discharge indicating that they were baroreceptors and thirty-five showed responses to stimuli indicating that they were arterial chemoreceptors. Twelve baroreceptor and thirteen chemoreceptor afferents had sufficiently stable unitary discharges to permit a detailed estimation of some of their central projections using stimulation through monopolar tungsten micro-electrodes to evoke antidromic spikes. In order to estimate their pattern of projection, depth-threshold contours for each penetration through the dorsomedial medulla and the values of antidromic latency were considered. Baroreceptor afferent fibres with myelinated (six units) and non-myelinated (six units) axons showed similar patterns of central projection. All could be activated from the ipsilateral nucleus of the tractus solitarius (n.t.s.), most often from its lateral divisions rostral to the obex. The dorsolateral and dorsomedial portions of the n.t.s. were most often innervated, with the commissural subnucleus receiving an innervation in seven of the twelve neurones studied. Stimulation of the ventrolateral subnucleus was effective in activating two afferent fibres whilst stimulation of the ventral subnucleus was effective in only one case. All chemoreceptor afferent fibres had calculated conduction velocities less than 4 m/s and all were activated from the dorsomedial and medial subnuclei of the ipsilateral n.t.s. In twelve of the thirteen neurones investigated in detail there was evidence of an innervation of the commissural nucleus both at the level of the obex and behind it. In three cases this extended into the contralateral portion of the commissural nucleus. In four cases a sparse innervation of the lateral subnucleus, comprising its dorsolateral aspects, was seen. The potential significance of these distinctive patterns of projection of arterial baroreceptors and chemoreceptors is discussed in relation to cardiovascular and respiratory control.

Direct pathway from neurons in the ventrolateral medulla relaying cardiovascular afferent information to the supraoptic nucleus in the cat

In chloralose anesthetized cats experiments were done to electrophysiologically identify neurons in the ventrolateral medulla (VLM) which relay cardiovascular afferent information directly to the supraoptic nucleus (SON). Action potentials elicited antidromically by electrical stimulation of the SON were recorded from 69 histologically verified single units in the VLM. Single units responded with latencies corresponding to conduction velocities of 7.8 ± 0.6m/s. Of these units 26 were excited orthodromically by stimulation of the buffer nerves; 12 responded to stimulation of only the carotid sinus nerve, 7 responded to stimulation of only the aortic depressor nerve, and 7 responded to both buffer nerves. The axons of VLM units that responded to buffer nerves conducted at a significantly slower velocity than those of non-responsive units (5.7 ± 0.4and9.1 ± 0.8m/s, respectively). These data provide electrophysiological evidence of two different populations of VLM neurons which project directly to the SON, and suggest that the direct pathway from the VLM to the SON is involved in the release of vasopressin by SON neurons during activation of baroreceptor and chemoreceptor afferent fibers.

Interaction between norepinephrine and hypoxia on carotid body chemoreception in rabbits.

The effects of both bolus injection and constant infusion of various levels of norepinephrine (NE) on the activity of single-carotid chemoreceptor nerve fibers was studied in pentobarbital-anaesthetized rabbits under normoxic and hypoxic conditions. All animals were paralyzed and artificially ventilated. The dominant effect of NE was to excite carotid body chemoreceptor fibers in a dose-dependent fashion. There was an inverse relationship between the effect of NE on afferent fiber discharge and arterial O2 tension at all levels of exogenous NE above threshold levels. Propranolol (PROP) in sufficient dosage abolished the chemoreceptor response to NE and also markedly reduced the chemoreceptor response to hypoxia. These results support suggestions that beta-adrenergic receptors may be an integral part of the O2 chemosensory mechanism. They also demonstrate a nonadditive interaction between the effects of NE and hypoxia on the chemoreceptor afferent fibers. A reduction in resting discharge levels after infusion of PROP further suggests that endogenous catecholamines may contribute to carotid body chemoreceptor activity even under normoxic normocapnic conditions.

Influence of neonatally administered capsaicin on baroreceptor and chemoreceptor reflexes in the adult rat.

1 Baroreceptor and chemoreceptor reflex activity was studied in anaesthetized adult rats which had been treated neonatally with a single injection of capsaicin (50 mg/kg s.c.). 2 Pressor responses to bilateral carotid artery occlusion were significantly lower in capsaicin-treated rats compared with vehicle-treated controls. Pressor responses to intravenously injected noradrenaline were similar in the two groups of rats. 3 Resting respiratory minute volume and tidal volume were lower in anaesthetized capsaicin-treated animals than in vehicle-treated controls, but there was no significant difference in respiratory frequency. 4 The increases in respiration evoked by intravenous administration of the peripheral arterial chemoreceptor stimulant, sodium cyanide, or by breathing a hypoxic gas mixture, were significantly lower in capsaicin-treated rats compared with the controls. 5 It is concluded that baroreceptor and chemoreceptor reflex activity are significantly reduced in anaesthetized adult rats which had been treated neonatally with capsaicin, and that this is likely to result from the destruction of unmyelinated baro- and chemoreceptor afferent fibres.

Actions of piperidine and dimethylphenylpiperazinium (DMPP) on afferent discharges of the cat's carotid body

Chemoreceptor discharges were recorded in vivo from fine filaments of carotid sinus nerve; their frequency was used as index of receptor activity. Effects of piperidine on chemoreceptors were studied and compared with those of dimethylphenylpiperazinium (DMPP) on chemoreceptors in adult cats. Intracarotid-arterial injections of piperidine produced a transient increase in chemoreceptor discharges, the threshold dose ranging from 10 to 50 μg i.a. The excitatory effect of piperidine was not affected by atropine, heamethonium or GABA. DMPP (0.2–0.5 μ i.a.) induced a marked increase in chemoreceptor discharges, which was abolished by hexamethonium, but not by atropine. DMPP (2–5 μg i.a.) induced sinus baroreceptor excitation, but piperidine did not. The results indicate that piperidine exerted excitatory effects on carotid body chemoreceptors, possibly acting on nerve endings of chemoreceptor afferent fibers.

Stimulus interaction in the responses of carotid body chemoreceptor single afferent fibers

The characteristics of steady-state responses of single afferent fibers of carotid chemoreceptors to independent changes in arterial P O 2 , and P CO 2 ; were investigated in cats. The arterial blood pressure was maintained within the normal limits (115–130 torr). Single chemoreceptor afferent fibers responded to changes both in arterial P O 2 and P CO 2 . The relationship between the activity of chemoreceptors and changes in arterial P CO 2 was linear at a constant arterial P CO 2 . The two stimuli showed multiplicative interaction. The activity approached zero (threshold) as arterial P CO 2 was decreased at a constant arterial P CO 2 a decrease in arterial pq, decreased the arterial Pco, threshold. These response characteristics of a single fiber suggest that the sensory receptor may be activated through a single mechanism by the two stimuli. The data fit into an idea that the mechanism may involve a conformational change in the membrane-bound polymeric chromophore group which reacts with O 2 reversibly and shows a Bohr-shift.

Effects of mecamylamine on responses of carotid body chemoreceptors in vivo to physiological and pharmacological stimuli.

1. Effects of mecamylamine on the spontaneous discharge rate of afferent fibres of carotid body chemoreceptors in vivo and their responses to ACh, NaCN, HCl and hypoxia were studied in sixteen cats.2. Cats were anaesthetized with sodium pentobarbitone, paralysed with gallamine triethiodide and artificially ventilated. Chemoreceptor excitants were injected into the common carotid artery; mecamylamine was given intravenously.3. Mecamylamine, 230 mug/kg or greater, failed to diminish either the rate of spontaneous discharge of carotid body chemoreceptors at high arterial oxygen tensions (greater than 130 mm Hg), or the responses of these receptors to NaCN (0.5-25 mug), HCl or hypoxic blood.4. Responses of chemoreceptor afferent fibres to ACh (1.0-50 mug) in the same preparations were either completely abolished or considerably reduced by mecamylamine.5. These data do not support the hypothesis of a cholinergic mechanism for the initiation of chemosensory discharges in the carotid body, either at rest or in response to stimuli such as NaCN, acid or hypoxia.

The frequency of nerve impulses in single carotid body chemoreceptor afferent fibres recorded in vivo with intact circulation.

1. The responses of single afferent fibres of carotid body chemoreceptors to independent changes in arterial O(2) and CO(2) tensions and pH were studied in the cat in vivo.2. The response curve obtained relating chemoreceptor activity to changes in arterial P(O2) was similar to an hyperbola; the frequency of nerve impulses at first decreased rapidly as the P(a,O2) was raised and then more slowly. The arterial P(O2) at which the slow decrease was reached varied among the different fibres; the mean level was 190 mm Hg (S.D. +/- 40 mm Hg).3. Single chemoreceptor afferent fibres continued to discharge even when the arterial P(O2) was more than 600 mm Hg.4. The discharges of single chemoreceptor afferent fibres increased both with increasing P(a,CO2) at constant pH and P(a,O2), and with increasing arterial H(+) at constant P(a,CO2) and P(a,O2).5. It is concluded that single carotid body chemoreceptor afferent fibres of the cat can be activated in vivo by an increase in either arterial H(+) or arterial P(CO2) as well as by a decrease in arterial P(O2).

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.