Stimulation Of Carotid Body Chemoreceptors Research Articles

Regulation of heart rate in vertebrates during hypoxia: A comparative overview.

Acute exposure to low oxygen (hypoxia) places conflicting demands on the heart. Whilst an increase in heart rate (tachycardia) may compensate systemic oxygen delivery as arterial oxygenation falls, the heart itself is an energetically expensive organ that may benefit from slowing (bradycardia) to reduce work when oxygen is limited. Both strategies are apparent in vertebrates, with tetrapods (mammals, birds, reptiles, and amphibians) classically exhibiting hypoxic tachycardia and fishes displaying characteristic hypoxic bradycardia. With a richer understanding of the ontogeny and evolution of the responses, however, we see similarities in the underlying mechanisms between vertebrate groups. For example, in adult mammals, primary bradycardia results from the hypoxic stimulation of carotid body chemoreceptors that are overwhelmed by mechano-sensory feedback from the lung associated with hyperpnoea. Fish-like bradycardia prevails in the mammalian foetus (which, at this stage, is incapable of pulmonary ventilation), and in fish and foetus alike, the bradycardia ensues despite an elevation of circulating catecholamines. In both cases, the reduced heart rate may primarily serve to protect the heart. Thus, the comparative perspective offers fundamental insight into how and why different vertebrates regulate heart rate in different ways during periods of hypoxia.

Nitric oxide infused in the solitary tract nucleus blocks brain glucose retention induced by carotid chemoreceptor stimulation

Previous work has shown that the carotid body glomus cells can function as glucose sensors. The activation of these chemoreceptors, and of its afferent nucleus in the brainstem (solitary tract nucleus – STn), induces rapid changes in blood glucose levels and brain glucose retention. Nitric oxide (NO) in STn has been suggested to play a key role in the processing of baroreceptor signaling initiated in the carotid sinus [1]. However, the relationship between changes in NO in STn and carotid body induced glycemic changes has not been studied. Here we investigated in anesthetized rats how changes in brain glucose retention, induced by the local stimulation of carotid body chemoreceptors with sodium cyanide (NaCN), were affected by modulation of NO levels in STn. We found that NO donor sodium nitroprusside (SNP) micro-injected into STn completely blocked the brain glucose retention reflex induced by NaCN chemoreceptor stimulation. In contrast, NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) increased brain glucose retention reflex compared to controls or to SNP rats. Interestingly, carotid body stimulation doubled the expression of nNOS in STn, but had no effect in iNOS. NO in STn could function to terminate brain glucose retention induced by carotid body stimulation. The work indicates that NO and STn play key roles in the regulation of brain glucose retention.

Effects of carotid sinus nerve transection on changes in neuropeptide Y and indolamines induced by long-term hypoxia in rats.

Long-term hypoxia induces changes in neuropeptide-Y-like immunoreactivity (NPY-LI) and/or in the content of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) at the central level. To determine whether these alterations depend on the integrity of carotid body (CB) chemoreceptors, intact rats or those whose carotid sinus nerve was transected (CSNT) were exposed to hypoxia (10% O2) or to normoxia for 14 days. Thereafter, NPY-LI, 5-HT and 5-HIAA levels in discrete brain regions were determined. The increase in NPY-LI in the ventrolateral medulla oblongata (VLM) of intact hypoxic rats was mostly abolished after CSNT and therefore is mainly mediated by CB chemoreceptors. In contrast, other hypoxia-induced changes were similar or even enhanced in CSNT as compared to intact rats and therefore do not depend on the integrity of CB chemoreceptors. This was the case for the increase of NPY-LI in the striatum and the caudal dorsomedian medulla oblongata (DMM), as well as for all the changes in 5-HT and 5-HIAA in the DMM, the VLM, the raphe nuclei, the striatum and the frontal cortex. We propose that long-term hypoxia alters brain NPY-LI and indolamine content through the stimulation of CB chemoreceptors or ancillary chemoreceptors, as well as through local biochemical or morphological mechanisms.

The effect of chemoreceptor stimulation on the centripetal transfer of somatosensory information in the urethane-anaesthetized rat

In urethane-anaesthetized rats, stimulation of carotid body chemoreceptors desynchronizes the cortical electroencephalogram and increases the sensitivity of thalamic and cortical somatosensory neurones to peripheral sensory nerve stimulation. Peripheral chemoreceptors were stimulated by injecting a bolus (30 ml) or infusing 100 ml of 0.18 M NaCl solution equilibrated with 100% CO 2 into an internal carotid artery, the cortical electroencephalogram and ventilation were monitored routinely. This stimulus induced hyperventilation and desynchronization of the cortical electroencephalogram. Anaesthetized rats also showed spontaneous periodic increases in ventilation rate accompanied by changes of the cortical electroencephalogram from high-voltage low frequency to low-voltage high frequency which seemed to be identical with those evoked by stimulating chemoreceptors. The activity of identified somatosensory neurons in the thalamic ventrobasal complex, layer IV of the somatosensory cortex, or the cuneate nucleus was recorded extracellularly during and following chemoreceptor activation. Neurones in the ventrobasal thalamus and somatosensory cortex showed a decrease in latency and an increase in probability of discharge to supramaximal electrical stimulation of the forepaw which was more pronounced following infusion stimulation of the carotid body than following bolus stimulation. In contrast, neurons within the cuneate nucleus showed a slight increase in latency to onset and a decrease in the probability of firing following the same stimulus. The results indicate that stimulation of the carotid body chemoreceptors leads to an enhancement of the response of somatosensory neurons to their normal physiological input.

Convergence properties of solitary tract neurones driven synaptically by cardiac vagal afferents in the mouse.

1. Cardiac vagal receptors are chemically and/or mechanically sensitive but it is unknown if this information is preserved centrally within the nucleus of the solitary tract (NTS). The present study had two aims: first, to investigate qualitatively whether both mechanically and chemically sensitive cardiac vagal encoding were preserved within the NTS, and second, to determine the patterns of convergence from other cardiorespiratory afferents to NTS neurones receiving cardiac vagal inputs. 2. The extracellular activity of single NTS neurones was investigated during stimulation of both chemically and mechanically sensitive cardiac vagal receptors in a working heart-brainstem preparation of mouse. Chemically sensitive cardiac receptors were stimulated using intra-left ventricular injections of either veratridine (1-3 microg kg-1), bradykinin (0.25-1 microg) or prostaglandin E2 (100-200 ng), whereas the left ventricle was distended to activate cardiac mechanoreceptors. 3. Forty-three NTS neurones were activated both synaptically by electrical stimulation of the ipsilateral vagus nerve (latency, 35 +/- 3 ms), and by intra-left ventricular injection of veratridine and also, in some cases, by bradykinin and/or PGE2. These NTS neurones were delineated into two populations based on their response to left ventricular distension and convergence properties. Left ventricular distension-insensitive neurones (n = 30) were excited by stimulation of carotid body chemoreceptors (81 %) but not arterial baroreceptors (3 %; i.e. n = 1 neurone), whereas distension-sensitive cells (n = 13) were activated mainly by baroreceptors (86 %) rather than peripheral chemoreceptors (14 %; i.e. n = 1 neurone). 4. The data reveal two distinct populations of NTS neurones receiving cardiac vagal inputs: (a) cells responsive to veratridine stimulation only, and (b) neurones activated by both veratridine and mechanical stimuli. The specific convergence pattern of baroreceptors and chemoreceptors to these cardioreceptive NTS neurones is discussed in relation to a common afferent modality integration within the NTS.

Effects of halothane on the phrenic nerve responses to carbon dioxide mediated by carotid body chemoreceptors in vagotomized dogs.

Previous studies in dogs showed that the phrenic nerve response to an acute hypoxic stimulus was dose dependently depressed by 0.5-2.0 minimum alveolar concentration (MAC) of halothane but not abolished. Because a carbon dioxide stimulus is transduced by a different mechanism in the carotid body chemoreceptors (CBCRs) than is a hypoxic stimulus, inhalational anesthetics may preferentially depress one of these transduction processes, the central neuronal processing, or both, of the integrated responses to these two types of inputs. Carotid body chemoreceptor stimulation was produced by short (1-1.5 s), bilateral, 100% carbon dioxide in saline infusions into the carotid arteries during neural inspiration in unpremedicated, halothane-anesthetized, paralyzed, vagotomized dogs during constant mechanical ventilation. The phrenic neurogram quantified the neural inspiratory response. Four protocols were performed in the study: (1) the dose-dependent effects of halothane anesthesia (0.5-2.0 MAC) during hyperoxic hypercapnia on phrenic nerve activity, (2) the effects of three background levels of the partial pressure of carbon dioxide (PaCO2) on the magnitude of the carbon dioxide infusion responses at 1 MAC halothane, (3) the effects of anesthetic type on the magnitude of the carbon dioxide infusion response, and (4) the effects of CBCR denervation. Peak phrenic nerve activity (PPA) increased significantly during the carbon dioxide-stimulated phrenic burst in protocols 1-3; after denervation there was no response (protocol 4). Halothane produced a dose-dependent reduction in the PPA of control and carbon dioxide infusion-stimulated phrenic bursts and in the net carbon dioxide response. The net PPA responses for the different PaCO2 background levels were not different but were somewhat larger for sodium thiopental anesthesia than for 1.0 MAC halothane. The phrenic nerve response to an acute, severe carbon dioxide stimulus was dose dependently depressed by surgical doses of halothane. The observed responses to carbon dioxide infusion were mediated by the CBCRs because they were eliminated by CBCR denervation. These results suggest that the CBCR transduction and central transmission of the carbon dioxide signal in terms of inspiratory excitatory drive are not abolished at surgical levels of halothane anesthesia.

Excitatory Amino Acid Receptors in the Paraventricular Hypothalamic Nucleus Mediate Pressor Response Induced by Carotid Body Chemoreceptor Stimulation in Rats

In urethane-anesthetized rats with spinal transection, antagonists of excitatory amino acid receptors, P2 purinoceptors and adrenoceptors were microinjected into the paraventricular hypothalamic nucleus (PVN) and their effects on the pressor response evoked by carotid body chemoreceptor stimulation were examined. Microinjections of the non-selective excitatory amino acid antagonist kynurenate, the non-NMDA receptor antagonist CNQX and the NMDA antagonist 2-

Nitric oxide synthase isoforms and peripheral chemoreceptor stimulation in conscious rats.

To test the effect of nitric oxide synthase (NOS) blockade on the ventilatory responses to carotid body chemoreceptor stimulation in freely behaving animals, chronically instrumented adult Sprague-Dawley rats received increasing intravenous doses of sodium cyanide (NaCN; 0-300 micrograms kg-1) before and after i.v. administration of either 100 mg kg-1 N-nitro-L-arginine methyl ester (L-NAME), a non-specific NOS blocker, or 10 mg kg-1 S-methyl-L-thiocitrulline (SMTC), a selective neuronal NOS inhibitor. SMTC did not modify the NaCN dose-response curve. In contrast, L-NAME significantly enhanced the ventilatory responses to NaCN. Western blots of equivalent amounts of protein from carotid body tissue homogenates revealed higher levels of endothelial NOS than of neuronal NOS. We conclude that endothelial NOS provides the major source for NO within the carotid body, and exerts a down-regulatory effect upon peripheral chemoreceptor responsivity.

Excitatory amino acid receptors in the rostral ventrolateral medulla mediate hypertension induced by carotid body chemoreceptor stimulation

The rostral ventrolateral medulla (RVLM) is involved in the mediation of cardiovascular responses to peripheral chemoreceptor stimulation. To investigate whether excitatory amino acid inputs in the RVLM are related to the responses to chemoreceptor stimulation, we microinjected kynurenate, an amino acid antagonist, unilaterally into the RVLM and examined its effects on the pressor response to stimulation of carotid body chemoreceptors. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. The carotid chemoreceptors were stimulated with isotonic solutions of inorganic phosphate solution. Stimulation of carotid body chemoreceptors produced increases in blood pressure. Kynurenate injected ipsilaterally but not contralaterally into the RVLM markedly inhibited the pressor response to chemoreceptor stimulation. In rats with spinal transection, stimulation of carotid body chemoreceptors also produced increases in blood pressure. The pressor response in rats with spinal transection was inhibited by intravenous injection of a vasopressin antagonist or by kynurenate injected ipsilaterally into the RVLM. Kynurenate injected into the RVLM inhibited the pressor response to NMDA, AMPA and kainate but not to acetylcholine in intact rats. These findings indicate that excitatory amino acid receptors are involved in mediating the pressor response to carotid body chemoreceptor stimulation in the rat RVLM. It appears that the chemoreceptor stimulation produces an increase in vasopressin release and the enhancement of vasopressin release is also mediated by an increase in excitatory amino acid inputs in the RVLM.

Cardiovascular and respiratory effects of adenosine in humans after pulmonary denervation.

Adenosine infusion causes tachycardia in normal subjects. A proposed mechanism is secondary pulmonary stretch receptor activation due to hyperventilation, induced by direct stimulation of carotid body chemoreceptors by adenosine. We examined responses to adenosine (incremental doses given by intravenous infusion, 5 min each rate) in six normal volunteers and six lung-transplant recipients with pulmonary denervation. Adenosine caused chemoreceptor stimulation in both groups with minute ventilation increasing from 5.8 +/- 0.4 to 10.7 +/- 1.3 l/min (P < 0.05) in the volunteers and from 4.8 +/- 0.4 to 9.2 +/- 0.8 l/min (P < 0.001) in the lung-transplant recipients. There was no difference in the magnitude of the ventilatory increase between the two groups (P = NS at all infusion rates). Adenosine produced tachycardia in both groups, with heart rate increasing from 66 +/- 5 to 84 +/- 3 beats/min (P < 0.01) in the volunteers and from 82 +/- 6 to 110 +/- 6 beats/min (P < 0.05) in the lung-transplant recipients. There was no difference in the magnitude of the heart rate response between the two groups (P = NS at all infusion rates). These data suggest, contrary to previous thinking, that pulmonary stretch receptor activation does not contribute to adenosine-induced tachycardia in humans.

Formula omitted] receptors but not [formula omitted] receptors mediate hypertension induced by carotid body chemoreceptor stimulation in the rostral ventrolateral medulla of the rat

In urethane-anesthetized rats, excitatory amino acid antagonists were microinjected into the rostral ventrolateral medulla (RVLM) and their effects on the pressor response and tachycardia evoked by carotid chemoreceptor stimulation were examined. Microinjections of the N- methyl- d-aspartate (NMDA) receptor antagonists 2-amino-5-phosphonovalerate (AP5) and MK-801 into the RVLM inhibited these chemoreceptor reflex responses whereas these responses were not affected by injection of the non-NMDA receptor antagonist CNQX. AP5 and MK-801 but not CNQX abolished the pressor response evoked by NMDA whereas CNQX but not AP5 and MK-801 abolished that evoked by AMPA or kainate. These results provide evidence that NMDA receptors in the RVLM of the rat are involved in the carotid chemoreceptor reflex.

Reflex control of the tracheal vasculature of sheep.

Arteries to the cervical trachea were perfused at constant flow in anesthetized sheep. Perfusion pressures (PP), blood pressure (BP), and changes in tracheal smooth muscle tone (Ptr) were measured. Stimulation of pulmonary C-fiber receptors decreased PP (-6.5%) and BP (-16.8%) and increased Ptr (+61.5%), changes prevented by vagotomy and therefore reflex. Stimulation of cardiac receptors and slowly adapting pulmonary stretch receptors decreased PP (-7.9%) and BP (-21.0) and increased Ptr (+19.0%), changes reversed by vagotomy and therefore reflex. Stimulation and inhibition of slowly adapting pulmonary stretch receptors had no vagal-dependent effect on PP and BP, but inflation decreased (-20.3%) and deflation increased Ptr (+35.2%), effects abolished by vagotomy and therefore reflex. Systemic hypoxia increased PP and BP before and after vagotomy (+12.2 and +40.3%), effects greatly reduced by cutting the carotid body nerves; it increased Ptr (+29.8%), an effect abolished by vagotomy and cutting the carotid body nerves. Systemic hypercapnia increased PP (+16.9%), BP (+20.5%), and Ptr (+36.2%), the first two responses being unaffected by vagotomy and the last almost abolished. Stimulation of carotid body chemoreceptors by KCN increased PP (+22.5%), BP (+104.7%), and Ptr (+8.5%), all responses prevented by cutting the carotid body nerves. Responses to intravenous injections of KCN were similar.

Reflex carotid body chemoreceptor control of phrenic sympathetic neurons

The reflexes reaction of phrenic sympathetic neurons to stimulation of carotid body chemoreceptors we tested in chloralos-anaesthetized and paralyzed cats with both vago-aotic nerves cut. During systemic hypoxia (animals ventilated with 10% 2 in O_ 2 in N 2) the sympathsti phrenic nerve activity increased from 100% in the control to 269%. The increase was markedly attentuad after cutting both nerves, Reflex exciatotry response in phrenic sympathetic neurons with the latency of 150 msec was evoked by electrical stimulation of the right carotid sinus nerve (3 pulses of 0.2 msec, 333 Hz). The central transmission time of the reflex was about 90 msec. Injecting 0.1 ml of 1 M NaHCO 3 saturated with CO 2 (in order to activate carotid body chemoreceptors) into the right or left carotid sinus, evoked excitatory responses in sympathetic neuronsp regardless of the side. The stimulation of carotid body chemoreceptors also increased somatic phrenic nerve activity. The three methods applied to the stimulation of carotid body chemoreceptors produced increase of phrenic nerve sympathetic activity.

Neurochemical and molecular biological aspects on the resetting of the arterial chemoreceptors in the newborn rat.

The role of the carotid body chemoreceptors in the fetus and immediately newborn has been a matter of debate over the past decades. Studies on fetal sheep suggested that the chemoreceptors are active in utero (Barcroft and Karvonen, 1948; Itskovitz and Rudolph, 1982, 1987), and this was confirmed by direct recordings from the sinus nerve (Blanco et al., 1984). However, the chemoreceptor response to hypoxia was lower in the fetus than in the newborn lamb (Blanco et al., 1984). This is consistent with the observation that the strength of the chemoreflex response is increased in babies a few days after birth as compared to the immediately newborn (Hertzberg and Lagercrantz, 1987). Thus, the arterial chemoreceptors seem to adapt from the low PaO2 prevalent in utero and reset their sensitivity after birth, when arterial oxygen tension is rising. As a consequence, the chemoreceptors are quiescent during the first day or so after birth. Accordingly, onset of breathing after birth appear to be dependent on other drive mechanisms, e.g. thermal, visual and tactile stimuli. The postnatal resetting of the chemoreceptors has been hypothesized to be due to changes in neurotransmitter expression and turnover in the carotid body. Substance P and the catecholamines are currently among the most studied messenger molecules. Substance P-like immunoreactivity was found in nerve fibers prenatally, while immunoreactive cells were not seen until after birth in kittens (Scheibner et al., 1988). In the adult cat the stimulation of carotid body chemoreceptors by hypoxia, but not by hypercapnia, was blocked by a substance P-antagonist (Prabhakar et al., 1984, 1987). Dopamine, the most abundant catecholamine in the carotid body of most species, has been shown to modulate chemoreceptor activity (Cardenas and Zapata, 1981; see also Hellstrom et al., 1984). In the following we would like to discuss some experiments aiming to define the role of these two neurotransmitters in the carotid body.KeywordsTyrosine HydroxylaseCarotid BodyFetal SheepGanglion NodosumFetal LambThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Excitatory amino acid receptors in commissural nucleus of the NTS mediate carotid chemoreceptor responses

Stimulation of carotid body chemoreceptors by saline saturated with 100% CO2 elicited an increase in mean arterial pressure, respiratory rate, tidal volume, and minute ventilation (VE). Microinjections of L-glutamate into a midline area 0.5-0.75 mm caudal and 0.3-0.5 mm deep with respect to the calamus scriptorius increased VE. Histological examination showed that the site was located in the commissural nucleus of the nucleus tractus solitarii (NTS). The presence of excitatory amino acid receptors [N-methyl-D-aspartic acid (NMDA); kainate, quisqualate/alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and trans 1-amino-cyclopentane-trans-1,3-dicarboxylic acid (ACPD)] in this area was demonstrated by microinjections of appropriate agonists. Simultaneous blockade of NMDA and non-NMDA receptors by combined injections of DL-2-aminophosphonoheptanoate (AP-7; 1 nmol) and 6,7-dinitro-quinoxaline-2,3-dione (DNQX; 1 nmol) abolished the responses to stimulation of carotid body on either side. Combined injections of AP-7 and DNQX did not produce a nonspecific depression of neurons because the responses to another agonist, carbachol, remained unaltered. Inhibition of the neurons in the aforementioned area with microinjections of muscimol (which hyperpolarizes neuronal cell bodies but not fibers of passage) also abolished the responses to subsequent carotid body stimulation on either side.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular responses of conscious rats to carotid body chemoreceptor stimulation by intravenous KCN

In the present study we analyzed the cardiovascular, respiratory and behavioral responses evoked in rats by KCN. Hypertension, hyperpnea and alerting behavior were characteristic responses in unanesthetized animals. Selective denervation of aortic and carotid bifurcation areas confirmed the carotid body chemoreceptor (CBC) origin of these responses. Sino-aortic denervation, as well as selective carotid sinus denervation abolished the responses, while, after selective aortic denervation, the responses were not different from those of the control rats. The administration of prazosin abolished the hypertensive response but did not change the bradycardic response, whereas the administration of atropine eliminated the bradycardic response and potentiated the hypertensive response to KCN. Increasing doses of KCN (10–80 μg/rat) produced proportionally larger bradycardia, hypertension and hyperventilation. Slight attenuation of bradycardic responses to KCN were observed in rats under chloralose anesthesia, while marked depression of bradycardic responses were observed under pentobarbitone anesthesia. Both anesthetics changed the hypertensive responses to hypotensive responses. In conclusion, the cardiovascular, respiratory and behavioral responses to intravenous KCN are a good functional test to CBC stimulation in unanesthetized rats, producing simultaneously intense bradycardia with hyperventilation and behaviour responses.

Transmitter diversity in carotid body afferent neurons: Dopaminergic and peptidergic phenotypes

Hypoxie stimulation of carotid body chemoreceptors is conveyed to the brainstem by primary sensory neurons whose peripheral axons run in the carotid sinus nerve. While considerable attention has focused on defining chemical neuroregulators released by glomus cells in the carotid body, our understanding of the morphology, distribution and transmitter phenotype of these carotid body afferent neurons remains limited. Carotid body afferent neurons were labeled by microinjection of the retrograde tracer, Fluorogold, into the vascularly isolated rat carotid body. In addition, immunoelectron microscopy was used to correlate transmitter phenotype with ultrastructural features of afferent terminals in the carotid body. Our results indicate that 41% of all carotid body afferent neurons express tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, whereas 7% contain substance P. Tyrosine hydroxylase- and substance P-positive neurons constitute separate subpopulations of carotid body afferents, as these two phenotypes were not colocalized. Most of the tyrosine hydroxylase-containing carotid body afferent neurons were small- or medium-sized (mean cell diameter 15–20 μm) and located in the distal petrosal ganglion, whereas the majority of substance P-containing carotid body afferent neurons were medium- to large-sized (mean cell diameter 20–29 μm) and located in the proximal petrosal ganglion and jugular ganglion. These differences strengthen the notion that these catecholaminergic and peptidergic carotid body afferent neurons give rise to functionally distinct subsets of chemoafferent fibers. To further characterize the catecholaminergic phenotype expressed by tyrosine hydroxylase-positive cells in the petrosal ganglion, we examined the colocalization of tyrosine hydroxylase and DOPA decarboxylase, the dopamine-synthesizing enzyme. Eighty-six per cent of tyrosine hydroxylase-positive neurons in the distal petrosal ganglion also contained DOPA decarboxylase; as these cells do not express the norepinephrine-synthesizing enzyme, dopamine beta-hydroxylase, these data indicate that the catecholaminergic carotid body afferent neurons are dopaminergic. Finally, ultrastructural analysis of the peripheral processes of tyrosine hydroxylase-positive afferent terminals in the carotid body demonstrated endings in close opposition to Type I glomus cells, consistent with a role for dopaminergic afferent neurons in carotid body chemoreception. One possibility is that these cells, in addition to their role as afferents, constitute a morphologic substrate for dopaminergic “efferent” inhibition in the carotid body.

The effect of discrete stimulation of carotid body chemoreceptors on atrial natriuretic peptide in anaesthetized dogs.

1. In seven chloralose-anaesthetized and artificially ventilated beagles, the carotid sinus regions were vascularly isolated and perfused with either arterial or mixed (arterial and venous) blood (PO2 46.4 +/- 1.5 mmHg, mean +/- S.E.M.) to stimulate the chemoreceptors at constant flow and pressure. Cervical vagosympathetic trunks were ligated in all dogs, and gallamine triethiodide (2.0 mg kg-1 h-1, I.V.) was given in five dogs. Right atrial pressure was measured in all dogs, and left atrial pressure in four dogs. Mean aortic pressure was held constant (91.0 +/- 3.0 mmHg) by means of a reservoir connected to the animal via the common carotid and femoral arteries. Plasma atrial natriuretic peptide (ANP) was measured by radioimmunoassay and urinary sodium by flame photometry. 2. In seven dogs with mean carotid sinus pressure maintained at 96.0 +/- 4.3 mmHg, stimulation of the carotid chemoreceptors for 25 min produced significant increases in left atrial pressure of 41.2 +/- 3.3% (n = 4; P less than 0.005) from 5.4 +/- 0.6 cmH2O and of 30.9 +/- 4.5% (n = 7; P less than 0.002) in ANP from 31.6 +/- 2.1 pg ml-1. However, chemoreceptor stimulation produced significant decreases in urine flow rate of 26.1 +/- 1.9% (n = 9; P less than 0.001) from 0.29 +/- 0.03 ml min-1 (100 g kidney weight)-1 and sodium excretion of 29.0 +/- 2.3% (P less than 0.001) from 8.5 +/- 1.7 mumol min-1 (100 g kidney weight)-1 but right atrial pressure and heart rate did not change significantly. In three of the dogs, beta-adrenoceptor blockade by atenolol (2 mg kg-1, I.V.) greatly reduced the effects of chemoreceptor stimulation on plasma levels of ANP. 3. The results show, for the first time, that discrete stimulation of the carotid chemoreceptors caused an increase in plasma ANP levels, probably due to the reflex increase in atrial pressure that results from an inhibition of the cardiac sympathetic nerves, and an increase in venous return from a reduction of peripheral vascular capacitance.

Responses of rostroventrolateral medulla spinal vasomotor neurones to chemoreceptor stimulation in rats

The activity of spinal projecting ‘vasomotor’ neurones of the rostroventrolateral medulla (RVL) has been recorded in anaesthetised and paralysed rats. They responded to carotid body chemoreceptor stimulation (0.208 M NaH 2PO 4) with an increase in discharge that preceded an evoked increase in arterial blood pressure. This initial excitatory response was followed by a fall in discharge correlated to the rise in blood pressure. RVL neurones, which had equivalent sensitivity to baroreceptor inputs but no spinal projecting axons, failed to exhibit the initial excitatory response on chemoreceptor stimulation. These observations suggest that the pressor response to chemoreceptor stimulation is mediated, at least partially, by excitation of RVL-spinal ‘vasomotor’ neurones.

Hypoxia-induced bronchial responsiveness in awake sheep: role of carotid chemoreceptors

Hypoxia enhances bronchial responsiveness in sheep and dogs and we recently reported a similar effect in asthmatic subjects. Activation of a reflex arc due to stimulation of peripheral chemoreceptors has been suggested to explain this finding. We evaluated the contribution of carotid body chemoreceptors to hypoxia-induced bronchial responsiveness in conscious sheep. Incremental concentrations of aerosolized methacholine were given to each of seven sheep ventilated successively (in a random order) with a normoxic and a hypoxic gas mixture (15% O 2 in N 2), both before and after peripheral surgical chemodenervation. Hypoxia alone did not affect lung mechanics in intact or chemodenervated animals. Bronchial responsiveness to methacholine was significantly increased by hypoxia in intact sheep, as compared to chemodenervated sheep. We conclude that hypoxia has a stimulating effect on bronchial responsiveness in awake sheep similar to that seen in human patients with asthma. This increased responsiveness may be mediated by hypoxic stimulation of carotid body chemoreceptors, which in turn may influence the nervous control of airway calibre.