Carotid Body Chemosensory Research Articles

Crucial Role of the Carotid Body Chemoreceptors on the Development of High Arterial Blood Pressure During Chronic Intermittent Hypoxia.

Exposure to chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, produces autonomic and cardiorespirartory alterations, and leads to systemic hypertension. These alterations are associated with enhanced carotid body (CB) chemosensory and ventilatory hypoxic reflexes and a decrease baroreflex (BRS) efficiency. The aim of this study was to determine the therapeutic effect of CB ablation on the elevated arterial blood pressure, the reduced BRS and the potentiated ventilatory response induced by CIH in conscious rats. Arterial blood pressure (BP) was continuous measured by telemetry in male Sprague-Dawley rats exposed to CIH (5 % O(2), 12 times/h, and 8 h/day). After 21 days of CIH, the CBs were selectively cryodestroyed, and rats were kept one more week in CIH. Ventilatory responses to hypoxia were assessed by whole body plethysmography and spontaneous BRS measured by the sequence method. Exposure to CIH produces hypertension, increased the chemoreflex ventilatory hypoxic responses, and decreased BRS. The ablation of the CBs normalized the elevated BP, and the altered ventilatory response and BRS. Present results suggest that the CB play a crucial role in the development of high arterial pressure and autonomic alterations induced by CIH.

Enhanced carotid body chemosensory activity and the cardiovascular alterations induced by intermittent hypoxia.

The carotid body (CB) plays a main role in the maintenance of the oxygen homeostasis. The hypoxic stimulation of the CB increases the chemosensory discharge, which in turn elicits reflex sympathetic, cardiovascular, and ventilatory adjustments. An exacerbate carotid chemosensory activity has been associated with human sympathetic-mediated diseases such as hypertension, insulin resistance, heart failure, and obstructive sleep apnea (OSA). Indeed, the CB chemosensory discharge becomes tonically hypereactive in experimental models of OSA and heart failure. Chronic intermittent hypoxia (CIH), a main feature of OSA, enhances CB chemosensory baseline discharges in normoxia and in response to hypoxia, inducing sympathetic overactivity and hypertension. Oxidative stress, increased levels of ET-1, Angiotensin II and pro-inflammatory cytokines, along with a reduced production of NO in the CB, have been associated with the enhanced carotid chemosensory activity. In this review, we will discuss new evidence supporting a main role for the CB chemoreceptor in the autonomic and cardiorespiratory alterations induced by intermittent hypoxia, as well as the molecular mechanisms involved in the CB chemosensory potentiation.

Carotid body potentiation during chronic intermittent hypoxia: implication for hypertension.

Autonomic dysfunction is involved in the development of hypertension in humans with obstructive sleep apnea, and animals exposed to chronic intermittent hypoxia (CIH). It has been proposed that a crucial step in the development of the hypertension is the potentiation of the carotid body (CB) chemosensory responses to hypoxia, but the temporal progression of the CB chemosensory, autonomic and hypertensive changes induced by CIH are not known. We tested the hypothesis that CB potentiation precedes the autonomic imbalance and the hypertension in rats exposed to CIH. Thus, we studied the changes in CB chemosensory and ventilatory responsiveness to hypoxia, the spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and arterial blood pressure in pentobarbital anesthetized rats exposed to CIH for 7, 14, and 21 days. After 7 days of CIH, CB chemosensory and ventilatory responses to hypoxia were enhanced, while BRS was significantly reduced by 2-fold in CIH-rats compared to sham-rats. These alterations persisted until 21 days of CIH. After 14 days, CIH shifted the HRV power spectra suggesting a predominance of sympathetic over parasympathetic tone. In contrast, hypertension was found after 21 days of CIH. Concomitant changes between the gain of spectral HRV, BRS, and ventilatory hypoxic chemoreflex showed that the CIH-induced BRS attenuation preceded the HRV changes. CIH induced a simultaneous decrease of the BRS gain along with an increase of the hypoxic ventilatory gain. Present results show that CIH-induced persistent hypertension was preceded by early changes in CB chemosensory control of cardiorespiratory and autonomic function.

Ebselen prevents the carotid body chemosensory potentiation and reverses the hypertension induced by intermittent hypoxia (873.1)

Oxidative stress is associated with hypertension and enhanced carotid body (CB) chemosensory responses induced by chronic intermittent hypoxia (CIH), but the underlying mechanism is not fully understood. We tested if ONOO‐ is involved in the CB enhanced chemosensivity. Accordingly, we studied the effects of Ebselen, a specific ONOO‐ scavenger, on 3‐nitrotirosine immunoreactivity (3‐NT‐ir) in the CB, the chemosensory discharge and arterial blood pressure (BP) in rats exposed to CIH. Male Sprague‐Dawley rats were exposed to CIH (5% O2, 12 times/h, 8 h/day), BP was measured with telemetry and Ebselen was administrated using subcutaneous osmotic pumps (10 mg/Kg day). At the end of the experiments, CB chemosensory discharge was recording, and rats were perfused with parafolmaldehyde 4% for 3‐NT‐ir. CIH increased 3‐NT‐ir in the CB, enhanced the chemosensory responses to hypoxia, elevated BP during normoxia and potentiated the BP responses to hypoxia. Ebselen prevented the CIH‐induced CB chemosensory potentiation, and reversed the elevated BP and the potentiated pressor responses to hypoxia. Our results showed that 3‐NT formation caused by CIH, contributes to the CB chemosensory potentiation, and that ONOO‐ is involved in the CIH‐induced hypertension.Grant Funding Source: Supported by FONDECYT 1100405

Intermittent hypoxia: endothelin‐1 and hypoxic carotid body chemosensory potentiation

Intermittent hypoxia: endothelin‐1 and hypoxic carotid body chemosensory potentiation

Selective contribution of inflammation and oxidative stress to the cardiorespiratory and carotid body alterations following intermittent hypoxia

Chronic intermittent hypoxia (CIH), a main feature of obstructive sleep apnea, potentiates carotid body (CB) chemosensory and ventilatory hypoxic responses, and induces hypertension. These alterations are attributed to oxidative stress, since antioxidants prevent the enhanced chemosensory and ventilatory hypoxic responses and the hypertension. We tested if oxidative stressinduced upregulation of pro‐inflammatory cytokines TNF‐α and IL‐1β are involved in the CB and cardiorespiratory alterations during CIH. We studied the effects of ibuprofen (40 mg/Kg day) on TNF‐α, IL‐1β and 3‐nitrotyrosine (3‐NT) CB levels, chemosensory and ventilatory hypoxic responses, and blood pressure in male Sprague‐Dawley rats exposed to CIH (5%O2, 12 times/h for 8 h/day) for 21 days. CIH increased CB TNF‐α, IL‐1β and 3‐NT, enhanced chemosensory and ventilatory hypoxic responses, and led to hypertension. Ibuprofen prevented the increased TNF‐α and IL‐1β CB levels and cardioventilatory alterations, but not the enhanced chemosensory hypoxic response and 3‐NT accumulation. Contrarily, ascorbic acid prevented the increased CB cytokines and 3‐NT expression, the chemosensory and ventilatory potentiation, and the hypertension. Thus, present results show that CIH‐induced potentiation of CB chemosensory responses to hypoxia depends critically on the oxidative stress, but not on the increased TNF‐α and IL‐1β in the CB. Thus, we provide new evidence suggesting a plausible role for pro‐inflammatory cytokines in the control of breathing and arterial pressure during CIH acting through a CB independent pathway.Supported by FONDECYT 1100405

Changes in expression and activity of MnSOD and CuZnSOD in carotid body and adrenal medullary cells of rats exposed to chronic intermittent hypoxia.

Nitro‐oxidative stress is associated with hypertension and enhanced carotid body (CB) chemosensory responses induced by chronic intermittent hypoxia (CIH). Since, ROS levels are regulated by cytoplasmic (CuZnSOD) and mitochondrial (MnSOD) superoxide dismutases; it is plausible that changes in their expression or enzymatic activity due to tyrosine nitration may contribute to the chemosensory potentiation. We studied effects of CIH on 3‐nitrotyrosine (3‐NT), SODs levels and activities, and MnSOD nitration in CB and adrenal medullary cells from Sprague‐Dawley male rats exposed to CIH (5% O2, 12 times/h for 8 h/day) for 7 days. To determine the contribution of mitochondrial ROS to the chemosensory potentiation, we studied the effects of the mitochondrial targeted antioxidant MitoTEMPO on the CIH‐induced CB chemosensory potentiation. CIH increased the 3‐NT levels in the CB and adrenal cells, the MnSOD level and activity in the CB, but not in adrenal medullary cells. CuZnSOD levels did not increase in any tissue. MitoTEMPO treatment prevented the CIH‐induced CB chemosensory potentiation. These results indicate that mithochondrial ROS are crucial for the chemosensory potentiation, while the increased CB MnSOD level and activity may be the result of a compensatory mechanism to the increased oxidative stress.Supported by FONDECYT 1100405 & AT 24110172

The human carotid body transcriptome with focus on oxygen sensing and inflammation – a comparative analysis

The carotid body (CB) is the key oxygen sensing organ. While the expression of CB specific genes is relatively well studied in animals, corresponding data for the human CB are missing. In this study we used five surgically removed human CBs to characterize the CB transcriptome with microarray and PCR analyses, and compared the results with mice data. In silico approaches demonstrated a unique gene expression profile of the human and mouse CB transcriptomes and an unexpected upregulation of both human and mouse CB genes involved in the inflammatory response compared to brain and adrenal gland data. Human CBs express most of the genes previously proposed to be involved in oxygen sensing and signalling based on animal studies, including NOX2, AMPK, CSE and oxygen sensitive K+ channels. In the TASK subfamily of K+ channels, TASK-1 is expressed in human CBs, while TASK-3 and TASK-5 are absent, although we demonstrated both TASK-1 and TASK-3 in one of the mouse reference strains. Maxi-K was expressed exclusively as the spliced variant ZERO in the human CB. In summary, the human CB transcriptome shares important features with the mouse CB, but also differs significantly in the expression of a number of CB chemosensory genes. This study provides key information for future functional investigations on the human carotid body.

Hypoxic intensity: a determinant for the contribution of ATP and adenosine to the genesis of carotid body chemosensory activity

Excitatory effects of adenosine and ATP on carotid body (CB) chemoreception have been previously described. Our hypothesis is that both ATP and adenosine are the key neurotransmitters responsible for the hypoxic chemotransmission in the CB sensory synapse, their relative contribution depending on the intensity of hypoxic challenge. To test this hypothesis we measured carotid sinus nerve (CSN) activity in response to moderate and intense hypoxic stimuli (7 and 0% O(2)) in the absence and in the presence of adenosine and ATP receptor antagonists. Additionally, we quantified the release of adenosine and ATP in normoxia (21% O(2)) and in response to hypoxias of different intensities (10, 5, and 2% O(2)) to study the release pathways. We found that ZM241385, an A(2) antagonist, decreased the CSN discharges evoked by 0 and 7% O(2) by 30.8 and 72.5%, respectively. Suramin, a P(2)X antagonist, decreased the CSN discharges evoked by 0 and 7% O(2) by 64.3 and 17.1%, respectively. Simultaneous application of both antagonists strongly inhibited CSN discharges elicited by both hypoxic intensities. ATP release by CB increased in parallel to hypoxia intensity while adenosine release increased preferably in response to mild hypoxia. We have also found that the lower the O(2) levels are, the higher is the percentage of adenosine produced from extracellular catabolism of ATP. Our results demonstrate that ATP and adenosine are key neurotransmitters involved in hypoxic CB chemotransduction, with a more relevant contribution of adenosine during mild hypoxia, while vesicular ATP release constitutes the preferential origin of extracellular adenosine in high-intensity hypoxia.

VEGF up‐regulation and vascular area enlargement induced by intermittent hypoxia in the rat carotid body is not secondary to oxidative stress

Chronic intermittent hypoxia (CIH), a main feature of obstructive sleep apnea, potentiated the carotid body (CB) chemosensory responses to acute hypoxia, enlarges the vascular area and increased the VEGF expression in the CB. Since oxidative stress plays an essential role in the CIH‐induced CB chemosensory potentiation and by the fact that VEGF may be directly up‐regulated by oxidative stress, we hypothesized if the treatment with an antioxidant may impede the increased expression of VEGF and the enlarged vascular area in the CB of rats exposed to CIH. Thus, we tested the effects of ascorbic acid on the vascular area enlargement and the VEGF immunoreactivity (VEGF‐ir) in the CB of rats exposed to 5%O2, 12 times/hr for 8 hrs or sham condition for 21 days. We found that CIH increased VEGF‐ir and enlarged the vascular area in the CB by increasing the size of the blood vessels, although the number of blood vessels was unchanged. Ascorbic acid, which prevented the CB chemosensory potentiation to hypoxia failed to impede the vascular enlargement and the increased VEGF‐ir in the CB. Thus, our results suggest that CB vascular changes, including VEGF up‐regulation may result of the direct hypoxic stimulation during CIH exposure, and not secondary to the increased oxidative stress, which is involved in the potentiation of the CB chemosensory responses to hypoxia.Supported by FONDECYT 1100405

Carotid body inflammation and cardiorespiratory alterations in intermittent hypoxia

Chronic intermittent hypoxia (CIH), a main feature of obstructive sleep apnoea (OSA), increases hypoxic ventilatory responses and elicits hypertension, partially attributed to an enhance carotid body (CB) responsiveness to hypoxia. As inflammation has been involved in CIH-induced hypertension and chemosensory potentiation, we tested whether ibuprofen may block CB chemosensory and cardiorespiratory alterations induced by CIH in a rat model of OSA. We studied the effects of ibuprofen (40 mg · kg(-1) · day(-1)) on immunohistochemical interleukin (IL)-1β and tumour necrosis factor (TNF)-α levels in the CB, the number of c-fos-positive neurons in the nucleus tractus solitarii (NTS), CB chemosensory and ventilatory responses to hypoxia, and arterial blood pressure in male rats either exposed for 21 days to 5% O(2) (12 episodes · h(-1), 8 h · day(-1)) or kept under sham condition. CIH increased CB TNF-α and IL-1β and c-fos-positive neurons in the NTS, enhanced carotid chemosensory and ventilatory hypoxic responses, and produced hypertension. Ibuprofen prevented CB cytokine overexpression and CIH-induced increases in c-fos-positive neurons in the NTS, the enhanced hypoxic ventilatory responses and hypertension, but failed to impede the CB chemosensory potentiation. Results suggest that pro-inflammatory cytokines may contribute to the CIH-induced cardiorespiratory alterations, acting at several levels of the hypoxic chemoreflex and cardiovascular control pathways.

Chronic intermittent hypoxia-induced vascular enlargement and VEGF upregulation in the rat carotid body is not prevented by antioxidant treatment

Chronic intermittent hypoxia (CIH), a characteristic of sleep obstructive apnea, enhances carotid body (CB) chemosensory responses to hypoxia, but its consequences on CB vascular area and VEGF expression are unknown. Accordingly, we studied the effect of CIH on CB volume, glomus cell numbers, blood vessel diameter and number, and VEGF immunoreactivity (VEGF-ir) in male Sprague-Dawley rats exposed to 5% O(2), 12 times/h for 8 h or sham condition for 21 days. We found that CIH did not modify the CB volume or the number of glomus cells but increased VEGF-ir and enlarged the vascular area by increasing the size of the blood vessels, whereas the number of the vessels was unchanged. Because oxidative stress plays an essential role in the CIH-induced carotid chemosensory potentiation, we tested whether antioxidant treatment with ascorbic acid may impede the vascular enlargement and the VEGF upregulation. Ascorbic acid, which prevents the CB chemosensory potentiation, failed to impede the vascular enlargement and the increased VEGF-ir. Thus present results suggest that the CB vascular enlargement induced by CIH is a direct effect of intermittent hypoxia and not secondary to the oxidative stress. Accordingly, the subsequent capillary changes may be secondary to the mechanisms involved in the neural chemosensory plasticity induced by intermittent hypoxia.

Differential expression of pro-inflammatory cytokines, endothelin-1 and nitric oxide synthases in the rat carotid body exposed to intermittent hypoxia

The enhanced carotid body (CB) chemosensory response to hypoxia induced by chronic intermittent hypoxia (CIH) has been attributed to oxidative stress, which is expected to increase the expression of chemosensory modulators including chemoexcitatory pro-inflammatory cytokines in the CB. Accordingly, we studied the time-course of the changes in the immunohistological expression of TNF-α, IL-1β, IL-6, ET-1, iNOS, eNOS and 3-nitrotyrosine in the CB, along with the progression of enhanced CB chemosensory responses to acute hypoxia in male Sprague-Dawley rats exposed to CIH (5%O 2, 12 times/h per 8 h) for 7, 14 and 21 days. Exposure to CIH for 7 days resulted in a sustained potentiation of CB chemosensory responses to acute hypoxia, which persisted until 21 days of CIH. The chemosensory potentiation was paralleled by an increased 3-nitrotyrosine expression in the CB. On the contrary, CIH produced a transient 2-fold increase of ET-1 immunoreactivity at 7 days, a decrease in eNOS immunoreactivity, and a delayed but progressive increase of TNF-α, IL-1β and iNOS immunoreactivity, which was not associated with changes in systemic plasma levels or immune cell invasion within the CB. Thus, present results suggest that the local expression of chemosensory modulators and pro-inflammatory cytokines in the CB may have different temporal contribution to the CB chemosensory potentiation induced by CIH.

Histaminergic and dopaminergic traits in the human carotid body

Carotid body (CB) chemoreceptors are the main sensors detecting systemic hypoxia. Studies in animals revealed that dopamine and histamine may serve as transmitters between the chemoreceptor cells and the afferent nerve. To gain insight whether histamine and dopamine could play a role in the human CB and thus be important for the understanding of breathing disorders, we have investigated the chemosensory traits in human CBs from nine subjects of different ages obtained at autopsy. Immunohistochemistry revealed expression of histidine decarboxylase, vesicular monoamine transporter 2, histamine receptors 1 and 3 in virtually all chemosensory cells within the glomeruli of different ages. By contrast, catecholaminergic traits (tyrosine hydroxylase and vesicular monoamine transporter 1) were only detected in a subset of CB chemosensory cells at each age group while dopamine D2 receptors were expressed in the great majority of them. Our data suggest that histamine along with catecholamines may serve as transmitters between chemoreceptor cells and the afferent nerve in humans as well.

Modulatory effects of histamine on cat carotid body chemoreception

Histamine has been proposed to be an excitatory transmitter between the carotid body (CB) chemoreceptor (glomus) cells and petrosal ganglion (PG) neurons. The histamine biosynthetic pathway, its storage and release, as well as the presence of histamine H1, H2 and H3 receptors have been found in the CB. However, there is only indirect evidence showing the presence of histamine in glomus cells, or weather its application produces chemosensory excitation. Thus, we studied the histamine immunocytochemical localization in the cat CB, and the effects of histamine, and H1, H2 and H3 receptor blockers on carotid sinus nerve (CSN) discharge, using CB and PG preparations in vitro. We found histamine immunoreactivity in dense-cored vesicles of glomus cells. Histamine induced dose-dependent increases in CSN discharge in the CB, but not in the PG. The H1-antagonist pyrilamine reduced the CB responses induced by histamine, the H2-antagonists cimetidine and ranitidine had no effect, while the H3-antagonist thioperamide enhanced histamine-induced responses. Present data suggests that histamine plays an excitatory modulatory role in the generation of cat CB chemosensory activity.

Dynamic time-varying analysis of heart rate and blood pressure variability in cats exposed to short-term chronic intermittent hypoxia

Chronic intermittent hypoxia (CIH) contributes to the development of hypertension in patients with obstructive sleep apnea and animal models. However, the early cardiovascular changes that precede CIH-induced hypertension are not completely understood. Nevertheless, it has been proposed that one of the possible contributing mechanisms to CIH-induced hypertension is a potentiation of carotid body (CB) hypoxic chemoreflexes. Therefore, we studied the dynamic responses of heart rate, blood pressure, and their variabilities during acute exposure to different levels of hypoxia after CIH short-term preconditioning (4 days) in cats. In addition, we measured baroreflex sensitivity (BRS) on the control of heart rate by noninvasive techniques. To assess the relationships among these indexes and CB chemoreflexes, we also recorded CB chemosensory discharges. Our data show that short-term CIH reduced BRS, potentiated the increase in heart rate induced by acute hypoxia, and was associated with a dynamic shift of heart rate variability (HRV) spectral indexes toward the low-frequency band. In addition, we found a striking linear correlation (r = 0.97) between the low-to-high frequency ratio of HRV and baseline. CB chemosensory discharges in the CIH-treated cats. Thus, our results suggest that cyclic hypoxic stimulation of the CB by short-term CIH induces subtle but clear selective alterations of HRV and BRS in normotensive cats.

Is ATP a suitable co-transmitter in carotid body arterial chemoreceptors?

A review is presented on carotid body ATP content, effects and release, receptors involved and results of their block by purinergic antagonists, and the possibility of cholinergic-purinergic co-transmission in the carotid body. Glomus cells release ACh and ATP upon physiological stimulation. Both agents and their agonists have chemo-excitatory actions and their combined effects disappear upon blocking n-ACh and P2X receptors. Both ACh and ATP also are capable of exciting the somata of chemosensory neurons of petrosal ganglia. Although a combined cholinergic-purinergic block suppresses the chemosensory activity in neurons co-cultured with glomus cells and some carotid body preparations in vitro, basal chemosensory activity and chemosensory responses to hypoxic stimuli persist in cat carotid body preparations in situ and in vitro. Therefore, ATP is an effective excitatory agent for carotid body chemosensory activity, although less potent than ACh; their joint participation may contribute to -- but does not entirely explain -- the transfer of chemoreceptor excitation from glomus cells to sensory endings in carotid body.

Autonomic cardiovascular effects of brief exposure to chronic intermittent hypoxia detected using analysis of heart rate variability and spontaneous baroreflex sensitivity

Obstructive sleep apnea patients and chronic intermittent hypoxia (CIH) animal models present increased cardiovascular responses. Therefore, it is possible that increased chemoreflexes and decreased baroreflex sensitivity (BRS) would elicit sympathetic overactivity, inducing hypertension. We previously showed that exposure of cats to CIH for 4 days increases the carotid body chemosensory and ventilatory responses to hypoxia. Thus, we studied the effect of brief exposure to CIH in cats for 4 days on sympathetic tone and BRS, using spectral analysis of heart rate variability (HRV), blood pressure variability (BPV) and BRS determination with the sequence method. In anesthetized cats we evaluated the effect of acute hypoxia on heart rate and blood pressure. Data was digitized with a PowerLab 8SP A/D interface and stored in a PC computer. For HRV and BPV analysis, we used autoregressive methods for estimation of the spectral density at the low-frequency (LF, 0.025–0.15) and high-frequency (HF, 0.15–0.833) bands. We compared control (normoxic) cats with animals exposed to sham-CIH and CIH. We found that CIH-treated cats showed enhanced tachycardic responses to acute severe hypoxia, with reduced HRV and BRS. Our data suggests that CIH exposure for 4 days induced early autonomic changes that favor an enhanced sympathetic outflow and decreased baroreflex control on blood pressure. Supported by FONDECYT 1030330.

Carotid body chemosensory activity and ventilatory chemoreflexes in cats persist after combined cholinergic–purinergic block

Acetylcholine (ACh) and ATP have been proposed as excitatory co-transmitters operating at synapses between glomus cells and sensory nerve endings of the carotid body (CB). To test such hypothesis, we performed experiments on cats under pentobarbitone anesthesia and breathing spontaneously. Cholinergic and purinergic agonists and antagonists were given into one common carotid artery. Chemoreflex ventilatory changes initiated from the ipsilateral CB or chemosensory activity from the ipsilateral carotid nerve were recorded. Agonists ACh, nicotine, epibatidine, ATP, betagamma-methylene-ATP and gammaS-ATP induced transient chemoreflex enhancements of ventilation or increased chemosensory activity. When given in combination, mecamylamine and suramin suppressed both nicotine- and ATP-induced ventilatory chemoreflexes or chemosensory responses. However, neither chemoreflex hyperventilation induced by brief hypoxic exposures or steady-state hypoxic levels, nor chemosensory excitation elicited by these maneuvers were eliminated. Asphyxia-induced chemosensory excitation was not reduced by combined blockade of ACh and ATP receptors. Furthermore, ventilatory or chemosensory depression evoked by 100% O2 tests was unmodified, thus evidencing that basal chemosensory drive in normoxia was not suppressed by combined cholinergic-purinergic blockade. Therefore, although ACh and ATP may participate in chemoexcitation of the CB, their involvement fails to explain the origin of chemosensory discharges from synaptic transmission between glomus cells and chemosensory nerve endings of the CB.

Endothelins in the cat petrosal ganglion and carotid body: Effects and immunolocalization

In response to hypoxia, chemoreceptor cells of the carotid body (CB) release transmitters, which acting on the petrosal ganglion (PG) neuron terminals, increase the chemoafferent discharge. Additionally, vasoactive molecules produced within the CB may modulate hypoxic chemoreception by controlling blood flow and tissue PO 2. Endothelin-1 (ET-1) increases basal CB chemosensory discharges in situ, probably due to its vasoconstrictor action. However, the actions of ET-1 on PG neurons or its expression in the PG are not known. Using immunohistochemistry, we found that endothelin-like peptides are expressed in the cat PG and CB under normoxic conditions. Exogenous applications of ET-1 increased the chemosensory activity in the vascularly perfused CB but were ineffective on either the CB or PG superfused preparations, both of which are devoid of vascular control. Thus, our data indicate that the excitatory effect of ET-1 in the carotid chemoreceptor system appears to be mainly due to a vasoconstrictor effect in the CB blood vessels.