Chemoreceptor Tissue Research Articles

Carotid Body Tumor Excision with and without Carotid Artery Reconstruction: Equivalency of 30-Day Outcomes over 12 Years in the American College of Surgery National Surgical Quality Improvement Program (ACS-NSQIP) Database

Background: Carotid body tumors (CBTs) are rare benign tumors that arise from the chemoreceptor tissue located at the carotid bifurcation that require excision if symptomatic. Depending on the size and location of the tumor, the carotid artery may need to be repaired after resection. This study aims to assess whether CBT excision with artery resection had higher rates of 30-day postoperative outcomes compared with CBT excision without artery resection. Methods: This is a retrospective cohort study. Patients were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) registry from 2005 to 2017. They were divided into two groups, based on Current Procedural Terminology (CPT®) codes: group A had CBT excision without carotid artery excision (CPT code 60600) and group B with carotid artery excision (CPT code 60605). Patient demographic characteristics, co-morbidities, and 30-days postoperative outcomes were compared between the two groups. Categorical data were analyzed using Pearson’s X2 or Fisher exact tests and presented as proportions (percentages). Continuous data were analyzed using parametric or non-parametric tests as appropriate. Statistical significance was defined as p < 0.05. Statistical analysis was performed using the SPSS statistical software package. Results: A total of 463 patients were identified, 410 (88.4%) in group A and 53 (11.4%) in group B. Overall, there were 291 (62.9%) women. A higher proportion of women underwent CBT excision only, compared to men (91.1% [265/291] vs. 84.3% [145/172], p < 0.0001). Demographics and comorbidities were similar between groups. There was no significant difference in the 30-day postoperative outcomes. The reoperation rate was higher in group B (3.8% vs. 1.5%, p = 0.334), while the readmission rate was higher in group A (3.2% vs. 0% p = 0.269), and both were not significantly different. Overall morbidity and serious morbidity were higher in group B (7.5% vs. 5.9%, p = 0.626) and lower in group A (5.7% vs. 3.9%, p = 0.544), respectively, but were not significantly different. Operative time (mean, SD) was higher in group B (187 ± 107 vs. 138 ± 66 min, p < 0.001). However, the median (IQR) of hospital length of stay (LOS) was similar (2 [1, 4] vs. 2 [1, 3] days, p = 0.134). Conclusions: Overall, no difference was noted in the 30-day postoperative outcome between the two surgical approaches of CBT. However, operative time was longer when artery resection was performed. Further research to determine the factors predicting the need for carotid artery resection among patient gender is needed.

Hepatic metastatic paraganglioma 12\u2009years after retroperitoneal paraganglioma resection: a case report

BackgroundParagangliomas, also known as chemodectomas, are rare tumors arise from chemoreceptor tissue, and most commonly locate at the bifurcation of the common carotid, the jugular foramen, aortic arch, and retroperitoneum. Paragangliomas generally are considered to be benign tumors, and rarely produce local or distant metastases. Metastasis to liver is extremely rare.Case presentationWe report the case of a 39-year-old woman, who had undergone resection of a retroperitoneal paraganglioma at her local hospital for 12 years. She was referred to our hospital for further evaluation of a hepatic mass, which was misdignosed as hepatocellular carcinoma (HCC) and was treated by transarterial chemoembolization (TACE) in the local hospital 6 years ago. At admission, CT scan revealed a huge hypervascular mass with many feeding arteries, almost the same size as 5 years ago. Ultrasound-guided biopsy of the liver tumor was performed and immunohistochemical examination confirmed the diagnosis of hepatic metastatic paraganglioma. Though liver metastasis failed to achieve complete response or partial response to TACE treatment, it remained stable without progression during the 7-year follow-up.ConclusionParagangliomas are slow growing tumors and metastasis may develop decades after resection of the primary lesion. Long-term follow-up is necessary, and curative or palliative treatment should be considered to control symptoms, improve life quality, reduce complications and prolong survival.

Ageing of the carotid body.

The ageing process is characterized by a decline in several physiological functions resulting in a reduced capability to maintain homeostasis. The lowered homeostatic capacity seems to involve the carotid body (CB), whose role is to modulate ventilation and tissue oxygen supply. It thus plays a prime role in all ageing processes. Ageing causes marked changes in CB morphology. In older animals, it is enlarged and shows a concomitant decrease in the percentage of chemoreceptor tissue, as well as a proliferation of type II cells. The carotid glomitis is present with aggregates of lymphocytes and fibrosis of the lobules. Type I cells are dehydrated, with a profound vacuolization, a shrinking nucleus, and lipofuscin accumulation. With increased age, human CB shows a reduction in the number and volume of mitochondria, fewer synaptic junctions between glomi, along with a reduction in CB content of neurotransmitters, leading to a sort of 'physiological denervation'. Ageing could be interpreted as a cumulative result of oxidative damage to cells, which derives from aerobic metabolism. Moreover, metabolic rate is tightly correlated with life duration; thus a loss in mitochondrial function is one of the prime factors affecting CB ageing processes. The age-related reduction in synaptic junctions might be a self-protective mechanism through which cells buffer themselves against an accumulation of reactive oxygen species. The correlation between hypoxia and the life duration of CB cells remains an open question until how and why cells sense oxygen is understood.

CaV3.2 T-type Ca²⁺ channels in H₂S-mediated hypoxic response of the carotid body.

Arterial blood O2 levels are detected by specialized sensory organs called carotid bodies. Voltage-gated Ca(2+) channels (VGCCs) are important for carotid body O2 sensing. Given that T-type VGCCs contribute to nociceptive sensation, we hypothesized that they participate in carotid body O2 sensing. The rat carotid body expresses high levels of mRNA encoding the α1H-subunit, and α1H protein is localized to glomus cells, the primary O2-sensing cells in the chemoreceptor tissue, suggesting that CaV3.2 is the major T-type VGCC isoform expressed in the carotid body. Mibefradil and TTA-A2, selective blockers of the T-type VGCC, markedly attenuated elevation of hypoxia-evoked intracellular Ca(2+) concentration, secretion of catecholamines from glomus cells, and sensory excitation of the rat carotid body. Similar results were obtained in the carotid body and glomus cells from CaV3.2 knockout (Cacna1h(-/-)) mice. Since cystathionine-γ-lyase (CSE)-derived H2S is a critical mediator of the carotid body response to hypoxia, the role of T-type VGCCs in H2S-mediated O2 sensing was examined. Like hypoxia, NaHS, a H2S donor, increased intracellular Ca(2+) concentration and augmented carotid body sensory nerve activity in wild-type mice, and these effects were markedly attenuated in Cacna1h(-/-) mice. In wild-type mice, TTA-A2 markedly attenuated glomus cell and carotid body sensory nerve responses to hypoxia, and these effects were absent in CSE knockout mice. These results demonstrate that CaV3.2 T-type VGCCs contribute to the H2S-mediated carotid body response to hypoxia.

Carotid Body Tumor - A Case Reports

Carotid body tumor, an extra-adrenal paraganglioma, represents an uncommon entity arising in chemoreceptor tissue located at the carotid bifurcation. They commonly present as asymptomatic neck masses and careful preoperative evaluation is required to find out the functional and vascular status of these tumours. An unusual case of a large (70 × 50 × 45 mm) carotid body tumor of Shamblin type III in a 50 year old male is being presented here. The evaluation, management and the final outcome of this case of carotid body tumour is being reported here. DOI: http://dx.doi.org/10.3329/uhj.v8i1.11670 University Heart Journal Vol. 8, No. 1, January 2012

Progressive Facial Paralysis Secondary to a Rare Temporal Bone Tumor<subtitle>Glomus Faciale</subtitle>

P aragangliomas are slow-growing benign neoplasms arising from foci of neural crest– derived chemoreceptor tissue, paraganglia. Paragangliomas are most often discovered based on mass effect on nearby structures and are rarely functional outside of the adrenal gland. In the head and neck, paraganglia most commonly reside at the carotid bifurcation, the inferior ganglion region or cervical portion of the vagus nerve, the jugular bulb, and the middle ear cavity; thus, most are discovered in these locations. In the skull base, paraganglia in the area of the jugular bulb and along the cochlear promontory make glomus tympanicum and glomus jugulare the most frequently encountered paragangliomas. Although these 2 tumors are relatively common in the temporal bone, a primary paraganglioma of the fallopian canal, or glomus faciale, is rare. In fact, to our knowledge, only 8 reports exist. We describe the presentation, workup, and treatment of the ninth report in the literature.

Oxygen‐Sensitive Potassium Channels in Chemoreceptor Cell Physiology

The characterization of the molecular mechanisms involved in low-oxygen chemotransduction has been an active field of research since the first description of an oxygen-sensitive K(+) channel in rabbit carotid body (CB) chemoreceptor cells. As a result, a large number of components of the transduction cascade, from O(2) sensors to O(2)-sensitive ion channels, have been found. Although the endpoints of the process are analogous, the heterogeneity of the elements involved in the different chemoreceptor tissues precludes a unifying theory of hypoxic signaling, and it has been a source of controversy. However, when these molecular constituents of the hypoxic cascade are brought back to their physiological context, it becomes clear that the diversity of mechanisms is necessary to build up an integrated cellular response that demands the concerted action of several O(2) sensors and several effectors.

Right Atrial Chemodectoma With Atypical Chest Pain: A 6-Year Surgical Follow-Up

Paragangliomas are rare neoplasms of neural crest origin and arise from the chromaffin (pheochromocytomas) or chemoreceptor (chemodectomas) tissues. Patients with cardiac chemodectomas, hormonally inactive paragangliomas, may have chest pain or various obstructive or compressive symptoms, depending on the location of the tumor. We report the case of a right atrial chemodectoma causing atypical chest pain. The tumor was discovered at transthoracic echocardiography. Coronary angiography showed a vascular tumor fed by a branch of the circumflex artery. En bloc tumor resection was carried out under cardiopulmonary bypass, with an uneventful surgical course. After 6 years of follow-up, the patient remains asymptomatic and disease-free.

Carotid body tumor in a 13-year-old child: Case report and review of the literature

Carotid body tumor (CBT), an extra-adrenal paraganglioma, represents an uncommon entity arising in chemoreceptor tissue located at the carotid bifurcation. Only a few cases have been reported in the literature in the pediatric age group less than 14 years of age, primarily as case reports. Surgical excision is advisable in almost all ages, however, in childhood, it is known to carry risks and difficulties due to the smaller size of the involved anatomical structures. We report an unusual case of a large (50 x 43 x 30 mm) carotid paraganglioma of Shamblin type III in a 13-year-old female, living at high altitude until the age of 9 years. This cervical mass was present, but smaller in size, several years before admission. However, an intense hypoxic stimulus at high altitude for 2 months at the age of 13 years probably induced a fast growing period of the lesion. The tumor was removed en bloc with the involved carotid segments and vascular continuity was restored by means of a common carotid to internal carotid saphenous vein interposition graft. No malignant behavior or regional metastatic spread of the resected mass was demonstrated. Furthermore, no inheritance pattern between family members was confirmed. A clinical update on CBTs in childhood a propos of this case report is undertaken.

Comparative analysis of neonatal and adult rat carotid body responses to chronic intermittent hypoxia

Previous studies suggest that carotid body responses to long-term changes in environmental oxygen differ between neonates and adults. In the present study we tested the hypothesis that the effects of chronic intermittent hypoxia (CIH) on the carotid body differ between neonates and adult rats. Experiments were performed on neonatal (1-10 days) and adult (6-8 wk) males exposed either to CIH (9 episodes/h; 8 h/day) or to normoxia. Sensory activity was recorded from ex vivo carotid bodies. CIH augmented the hypoxic sensory response (HSR) in both groups. The magnitude of CIH-evoked hypoxic sensitization was significantly greater in neonates than in adults. Seventy-two episodes of CIH were sufficient to evoke hypoxic sensitization in neonates, whereas as many as 720 CIH episodes were required in adults, suggesting that neonatal carotid bodies are more sensitive to CIH than adult carotid bodies. CIH-induced hypoxic sensitization was reversed in adult rats after reexposure to 10 days of normoxia, whereas the effects of neonatal CIH persisted into adult life (2 mo). Acute intermittent hypoxia (IH) evoked sensory long-term facilitation of the carotid body activity (sensory LTF, i.e., increased baseline neural activity following acute IH) in CIH-exposed adults but not in neonates. The effects of CIH were associated with hyperplasia of glomus cells in neonatal but not in adult carotid bodies. These observations demonstrate that responses to CIH differ between neonates and adults with regard to the magnitude of sensitization of HSR, susceptibility to CIH, induction of sensory LTF, reversibility of the responses, and morphological remodeling of the chemoreceptor tissue.

Function of the rat carotid body chemoreceptors in ageing

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

CARDIOVASCULAR ALTERATIONS BY CHRONIC INTERMITTENT HYPOXIA: IMPORTANCE OF CAROTID BODY CHEMOREFLEXES

1. Humans experiencing intermittent hypoxia (IH) owing to recurrent apnoea syndromes exhibit serious cardiovascular morbidity, including high blood pressure, increased sympathetic nerve activity, cardiac arrhythmia and myocardial infarction. Although apnoeas are accompanied by a simultaneous decrease in arterial O(2) (hypoxia) and an increase in CO(2) (hypercapnia), studies on experimental animals suggest that hypoxia, rather than hypercapnia, is the primary stimulus for developing hypertension and enhanced sympathetic nerve activity. Enhanced hypoxic-sensing ability of the carotid bodies and the ensuing reflex activation of the sympathetic nervous system have been suggested to play a critical role in cardiorespiratory alterations resulting from recurrent apnoeas. 2. The purpose of the present review is to highlight recent studies demonstrating the effects of IH on carotid body sensory activity and its consequences on sympathetic activation in a rodent model of chronic IH. Adult rats exposed to chronic IH (15 s of 5% O(2) followed by 5 min of 21% O(2), nine episodes per h, 8 h/day for 10 days) exhibited selective enhancement of carotid body sensory response to hypoxia. In addition, chronic IH induced a novel form of sensory plasticity in the carotid body, manifested as sensory long-term facilitation (LTF). Functional changes in the carotid body occurred in the absence of morphological changes in the chemoreceptor tissue. 3. Acute hypoxia increased expiratory modulated splanchnic nerve activity (SNA) and acute IH-induced LTF in SNA. Hypoxia-induced SNA activation was prevented by bilateral sectioning of the sinus nerves. Rats exposed to chronic IH exhibited enhanced hypoxia-induced sympathetic activation and augmented LTF of the SNA. Bilateral sectioning of the sinus nerves abolished these responses, suggesting chronic IH-induced alterations in carotid body sensitivity contribute to LTF in SNA and the subsequent cardiovascular alterations.

Recombinant hTASK1 Is an O2-Sensitive K+ Channel

Hypoxic inhibition of background K+ channels is crucial to O2 sensing by chemoreceptor tissues, but direct demonstration of O2 sensitivity by any member of this K+ channel family is lacking. HEK293 cells were transfected with a pcDNA3.1-hTASK1 construct; expression of hTASK1 was verified using RT-PCR and immunocytochemistry. Whole-cell K+ currents of cells stably expressing hTASK-1 were, as anticipated, extremely sensitive to extracellular pH, within the physiological range (IC50 ≈ 7.0). All cells expressing this signature pH sensitivity were acutely modulated by pO2; reduction of pO2 from 150 to <40 mmHg (at pH 7.4) caused rapid and reversible suppression of pH-sensitive K+ currents. Furthermore, these two regulatory signals clearly acted at the same channel, since the magnitude of the O2-sensitive current was dependent on the extracellular pH. These data represent the first direct verification that hTASK1 is O2-sensitive and reinforce the idea that this K+ channel is key to O2 sensing in chemoreceptors.

NADPH Oxidase Does Not Account Fully for O2-Sensing in Model Airway Chemoreceptor Cells

A key feature of O2 sensing by chemoreceptor tissues is the hypoxic inhibition of K+ channels. However, mechanisms coupling a fall of pO2 to channel closure differ between tissues: O2 regulation of K+ channels in chemoreceptive neuroepithelial bodies and their immortal counterparts, H146 cells, involves altered reactive oxygen species generation by NADPH oxidase. In contrast, this enzyme complex is not involved in O2 sensing by the carotid body and pulmonary vasculature. Here, we provide pharmacological evidence to support a role for NADPH oxidase in hypoxic inhibition of K+ currents in H146 cells. Two structurally unrelated NADPH oxidase inhibitors, diphenylene iodonium and phenylarsine oxide, suppressed hypoxic inhibition of K+ currents recorded using the patch-clamp technique. Most importantly, however, neither inhibitor fully blocked this response. Our findings provide the first evidence that multiple mechanisms may coexist within a specific cell type to account for hypoxic suppression of K+ channel activity.

Paraganglioma of the Temporal Bone: Role of Magnetic Resonance Imaging versus Computed Tomography

Paragangliomas, also known as glomus tumors or chemodectomas, are tumors arising from chemoreceptor tissue (paraganglia), which are neural crest in origin and found in higher concentration along the glossopharyngeal and vagal cranial nerve. Three types of paragangliomas are related with the temporal bone: glomus tympanicum, glomus jugulare, and glomus vagale. The role of computed tomography (CT) and magnetic resonance imaging (MRI) in diagnosing these types of tumors is discussed, along with the importance of arteriography in aiding the diagnosis and treatment. This article discusses the choice between CT and MR based on clinical symptoms and tumor location, and illustrates the newest CT, MR, and angiography applications. A brief discussion on treatment options is given.

Peptidases of the peripheral chemoreceptors: biochemical, immunological, in vitro hydrolytic studies and electron microscopic analysis of neutral endopeptidase-like activity of the carotid body

The purposes of the present study are to identify and characterize the major peptidase(s) that may be involved in the inactivation of neuropeptides in the mammalian carotid body. Measurements of a number of peptidase activities in the cell-free extract of the cat carotid body using specific substrates and inhibitors indicated that the previously identified neutral endopeptidase (NEP)-like activity [Kumar et al., Brain Res., 517 (1990) 341–343] is the major peptidase in the chemoreceptor tissue. The NEP-like activity of the carotid body was further characterized using a monoclonal antibody to human neutral endopeptidase, EC 3.4.24.11. Immune blot analysis indicated strong immunoreactivity toward the cat and calf carotid bodies but a weak cross-reactivity with the rabbit carotid body. Furthermore, western blot analysis of the cat carotid body extract revealed the presence of a major 97-kDa protein and a minor 200-kDa protein. The 97-kDa NEP form of the carotid body was comparable to EC 3.4.24.11 and was consistent with its reported molecular weight suggesting NEP-like activity of the carotid body is structurally similar to the neutral endopeptidase, EC 3.4.24.11. In order to assess whether NEP is the primary peptide degrading activity in the cat carotid body in vitro hydrolysis studies using substance P (SP) as a model peptide were performed. HPLC analysis showed that SP is hydrolyzed maximally at pH 7.0 by carotid body peptidases with the formation of SP(1–7) and SP(1–8) as stable intermediates. Inhibitors specific to NEP also inhibited the SP-hydrolyzing activity of the carotid body. Analyses of the cell-free extracts showed the occurrence of both NEP and SP-hydrolyzing activities in the rabbit and rat carotid bodies although at 2- and 4-fold lower levels respectively than that observed in the cat carotid body. Immunoelectron microscopy showed that NEP-specific immunoreactivity is associated with the intercellular region between the type I cells and cell clusters of the carotid body. Taken together, the results from this investigation demonstrate that neutral endopeptidase (EC 3.4.24.11) is one of the major endopeptidases which mediates the degradation and inactivation of neuropeptides in the carotid body.

G proteins in carotid body chemoreception.

G proteins are signal coupling molecules that play major roles in mediating the effects of transmitters as well as certain sensory signals. In the present study we examined whether oxygen chemoreception in the carotid body is coupled to G proteins. Experiments were performed on carotid bodies isolated from anesthetized cats. Presence of G proteins was examined with ADP-ribosylation of the carotid body membranes. Pertussis toxin (PTX), which inactivates G proteins in neuronal tissues, ADP-ribosylated a single band of carotid body protein with a molecular mass of 41 kDa. With cholera toxin (CTX) only a faint band of protein corresponding to approximately 45 kDa was evident. Perfusing the isolated carotid bodies with PTX (2.5 micrograms/min; 60 min) attenuated the sensory response to hypoxia by 52% of the controls. Perfusion with CTX (50 micrograms/min; for 60 min), on the other hand, increased baseline activity and potentiated the hypoxic response by 125% of controls. Heat-inactivated toxins, however, had no influence on the carotid body sensory response to hypoxia. These results suggest that G proteins are present in the chemoreceptor tissue and they seem to be coupled to the transduction and/or to the transmission of the hypoxic stimulus.

Ultrastructural Changes in Nervous Elements associated with the Granular Cells of the Common Carotid Artery of the Domestic Fowl after Distal Vagal Ganglionectomy

Intramural granular cells of the left and right common carotid artery of the domestic fowl were examined with the electron microscope after left distal vagal ganglionectomy. The vast majority of the nerve fibers and endings associated with the granular cells of the left common carotid artery degenerated rapidly after ipsilateral ganglionectomy, indicating that they are derived from the left vagus. On the other hand, left distal vagal ganglionectomy resulted in transformation of the intramural granular cells of the right common carotid artery and the few nervous elements associated with them, into a typical chemoreceptor tissue. This tissue was made up of small granule (60-120 nm) containing cells associated with many nerve fibers, nerve endings and fenestrated capillaries. The nerve endings were of two types; presumptive afferent endings and adrenergic efferent endings. Both types of endings made synaptic junctions with the granular cells.

Selective inhibition of the carotid body sensory response to hypoxia by the substance P receptor antagonist CP-96,345.

Carotid bodies are sensory organs for monitoring arterial oxygen and CO2. Previous studies have shown that chemoreceptor tissue contains substance P (SP) and exogenously administered SP augments chemosensory discharge. In the present study, we examined the physiological importance of SP in carotid body chemoreception by using a selective nonpeptide SP [neurokinin (NK) 1] receptor antagonist CP-96,345. In experiments performed on anesthetized cats, sensory discharge was recorded from the carotid body in situ. To control for alterations in blood flow, additional studies were conducted on the carotid body in vitro. In in vivo studies, close carotid body (intraarterial) administration of CP-96,345 attenuated the sensory response to hypoxia in a dose-dependent manner with 73% of the response abolished at doses of 0.3-0.6 mg/kg. Comparable doses of the (2R,3R)-enantiomer had no effect on hypoxia-induced excitation, indicating that the effect of CP-96,345 was not due to nonspecific action. In contrast, the carotid body response to high CO2 was not affected by CP-96,345, implying that only the hypoxic response is mediated by NK-1 receptor and confirming that the effect of the SP antagonist was not due to nonspecific actions. Marked attenuation of the sensory response to hypoxia was also obtained in the carotid body in vitro, suggesting that the effects of the NK-1 antagonist were not secondary to cardiovascular changes. These results demonstrate that CP-96,345 attenuates or abolishes the chemosensory response to hypoxia but not to CO2 and suggest that SP mediates the hypoxia-induced sensory excitation in the cat carotid body via NK-1 receptor activation.

Nitric oxide in the sensory function of the carotid body

Recent studies suggest that nitric oxide (NO) may act as a chemical messenger in the nervous system. Since neurotransmitters are considered necessary for the sensory function of the carotid body, and molecular O 2 is a co-factor for NO synthesis, we examined whether (a) chemoreceptor tissue also synthesizes NO and if so, (b) does endogenous NO affect chemosensory activity. Experiments were performed on carotid bodies obtained from anesthetized cats ( n = 20). Distribution of nitric oxide synthase (NOS), an enzyme that catalyzes the formation of NO was examined using NADPH-diaphorase histochemistry. Many nerve plexuses innervating the chemoreceptor tissue were positive for NADPH-diaphorase, indicating that the nerve fibers are the primary source of NO production in the carotid body. Radiometric analysis of NOS activity of the chemoreceptor tissue averaged 1.94 pmol [ 3H]citrulline/min/mg protein. NOS activity was significantly less in low pO 2 reaction medium than in room air controls. Chemosensory activity in vitro increased in a dose-dependent manner in response to l-ω-nitro arginine ( l-NNA), an inhibitor of NOS activity. The effects of NOS inhibitor were enantiomer selective as evidence by reversal of the responses by l- but not d-arginine. These observations imply that endogenous NO is inhibitory to carotid body sensory activity. cGMP levels of l-NNA-treated carotid bodies were significantly less than untreated controls, suggesting that the actions of NO are coupled to the cGMP second messenger system, as elsewhere in the nervous system. Based on the findings that (a) low pO 2 decreased NOS activity and, (b) endogenous NO is inhibitory to the sensory discharge, it is suggested that the mechanism(s) of sensory excitation by hypoxia in the carotid body may involve ‘disinhibition’ inhibitory to the sensory discharge, it is suggested that the mechanism(s) of sensory excitation by hypoxia in the carotid body may involve ‘disinhibition’ resulting from NO synthesis.