The discovery of the sensory nature of the carotid body dates back to the beginning of the 20th century. Following these seminal discoveries, research into carotid body mechanisms moved forward progressively through the 20th century, with many descriptions of the ultrastructure of the organ and stimulus-response measurements at the level of the whole organ. The later part of 20th century witnessed the first descriptions of the cellular responses and electrophysiology of isolated and cultured type I and type II cells, and there now exist a number of testable hypotheses of chemotransduction. The goal of this article is to provide a comprehensive review of current concepts on sensory transduction and transmission of the hypoxic stimulus at the carotid body with an emphasis on integrating cellular mechanisms with the whole organ responses and highlighting the gaps or discrepancies in our knowledge. It is increasingly evident that in addition to hypoxia, the carotid body responds to a wide variety of blood-borne stimuli, including reduced glucose and immune-related cytokines and we therefore also consider the evidence for a polymodal function of the carotid body and its implications. It is clear that the sensory function of the carotid body exhibits considerable plasticity in response to the chronic perturbations in environmental O2 that is associated with many physiological and pathological conditions. The mechanisms and consequences of carotid body plasticity in health and disease are discussed in the final sections of this article.

Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body

The respiratory response to hypoxia in mammals develops from an inhibition of breathing movements in utero into a sustained increase in ventilation in the adult. This ventilatory response to hypoxia (HVR) in mammals is the subject of this review. The period immediately after birth contains a critical time window in which environmental factors can cause long-term changes in the structural and functional properties of the respiratory system, resulting in an altered HVR phenotype. Both neonatal chronic and chronic intermittent hypoxia, but also chronic hyperoxia, can induce such plastic changes, the nature of which depends on the time pattern and duration of the exposure (acute or chronic, episodic or not, etc.). At adult age, exposure to chronic hypoxic paradigms induces adjustments in the HVR that seem reversible when the respiratory system is fully matured. These changes are orchestrated by transcription factors of which hypoxia-inducible factor 1 has been identified as the master regulator. We discuss the mechanisms underlying the HVR and its adaptations to chronic changes in ambient oxygen concentration, with emphasis on the carotid bodies that contain oxygen sensors and initiate the response, and on the contribution of central neurotransmitters and brain stem regions. We also briefly summarize the techniques used in small animals and in humans to measure the HVR and discuss the specific difficulties encountered in its measurement and analysis.

The Ventilatory Response to Hypoxia in Mammals: Mechanisms, Measurement, and Analysis

Background The sleep apnea syndrome (SAS) is a common health problem with a 30% prevalence among patients with so-called essential hypertension. Objective Prompted by this epidemiologic link we tried to find out whether there is a cause-effect relationship between SAS and systemic hypertension. Design We developed an animal model to simulate defined aspects of the SAS. Rats were exposed to chronic repetitive hypoxia for 7 h per day and their blood pressure was measured by invasive methods. Results We found that 30 days of intermittent hypoxia sufficed for the development of a significant elevation of blood pressure. The co-exposure to hypoxia and hypercapnia had no additional effect. Surgical denervation of peripheral chemoreceptors prevented the increase in arterial blood pressure. Adrenal demedullation and chemical denervation of the peripheral sympathetic nervous system by 6-hydroxy dopamine also prevented the increase. Conclusions Our data imply that repetitive hypoxemia in SAS is probably the cause of the high prevalence of systemic hypertension in this population and that peripheral chemoreceptors and the sympathetic nervous system play important roles in this pathophysiologic process.

Hypertension caused by chronic intermittent hypoxia--influence of chemoreceptors and sympathetic nervous system

To investigate whether the transcriptional activator hypoxia-inducible factor 1 (HIF-1) is required for ventilatory responses to hypoxia, we analyzed mice that were either wild type or heterozygous for a loss-of-function (knockout) allele at the Hif1a locus, which encodes the O2-regulated HIF-1α subunit. Although the ventilatory response to acute hypoxia was not impaired in Hif1a+/− mice, the response was primarily mediated via vagal afferents, whereas in wild-type mice, carotid body chemoreceptors played a predominant role. When carotid bodies isolated from wild-type mice were exposed to either cyanide or hypoxia, a marked increase in sinus nerve activity was recorded, whereas carotid bodies from Hif1a+/− mice responded to cyanide but not to hypoxia. Histologic analysis revealed no abnormalities of carotid body morphology in Hif1a+/− mice. Wild-type mice exposed to hypoxia for 3 days manifested an augmented ventilatory response to a subsequent acute hypoxic challenge. In contrast, prior chronic hypoxia resulted in a diminished ventilatory response to acute hypoxia in Hif1a+/− mice. Thus partial HIF-1α deficiency has a dramatic effect on carotid body neural activity and ventilatory adaptation to chronic hypoxia.

http://www.pnas.org/content/99/2/821.full.pdf

Defective carotid body function and impaired ventilatory responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1α

The aging respiratory system--pulmonary structure, function and neural control.

The restoration of ventilatory responses to hypoxia after carotid body denervation was studied in twenty-eight awake rats. The respiratory depression seen in moderate hypoxia (partial pressure of inspired O2, PI,O2, 80-100 mmHg) 3 days after bilateral carotid sinus nerve section disappeared by day 10. By day 17 respiratory stimulation occurred at all levels of PI,O2 below 125 mmHg. The largest restored response, in severe hypoxia (PI,O2 50-60 mmHg), was approximately 55% of the pre-denervation response. The response showed little further change from day 17 to day 192. A comparison of the effect of bilateral section of the glossopharyngeal nerve and of the abdominal vagus 1 and 28 days after carotid sinus nerve section demonstrated that the restoration of hypoxic response resulted in part from an enhanced effect of the inputs from the secondary glomus tissue served by these nerves. A comparison of the effect of bilateral section of glossopharyngeal, abdominal vagal and aortic depressor nerves 1 and 28 days after carotid sinus nerve section demonstrated an increase of a residual hypoxic response which must result either from inputs from unidentified peripheral chemoreceptors or from central mechanisms. Bilateral sectioning of the aortic depressor nerves produced no additional effect on restored responses to sectioning glossopharyngeal and abdominal vagal nerves, providing further evidence against significant aortic body function in the rat. The studies support the hypothesis that central neural reorganization provides compensation for loss of carotid body function by enhancement of effects of normally subsidiary inputs.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1986.sp016272

Restoration of hypoxic respiratory responses in the awake rat after carotid body denervation by sinus nerve section.

Normoxic and hypoxic respiration has been measured in awake rats after denervation procedures designed to eliminate the regulatory input from the carotid bodies, from all chemosensory tissue supplied by the glossopharyngeal nerve (n. IX), and from abdominal chemoreceptors. Studies were made 1 day after section of the carotid sinus nerve (c.s.n.), n. IX (at a level including c.s.n.), the abdominal vagus (n. Xa) and combinations of these nerves. Results were compared with those found in normal controls. C.s.n. section led to hypoventilation in both normoxia and hypoxia, reductions in respiratory frequency being consistent and substantial, and reductions in tidal volume varying with the degree of hypoxia. By comparison, section of n. IX produced significantly greater reductions of both normoxic and hypoxic ventilation. Section of n. Xa produced no significant change in normoxic ventilation but in hypoxia produced a significant small reduction in ventilation, mostly from an effect on tidal volume. Denervation of all the associated chemosensory tissue by combined section of n. IX and n. Xa demonstrated a summation of effects but left two distinct residual responses, one to mild hypoxia, and one to severe hypoxia, both associated mainly with increases of tidal volume. The experiments demonstrate that glomus tissues at different sites in the rat produce significant and distinct contributions to respiratory regulation. Denervation of all known receptors shows that significant ventilatory responses to hypoxia are still produced, either by unrevealed peripheral chemoreceptors, or by central neural mechanisms.

Respiratory effects of sectioning the carotid sinus glossopharyngeal and abdominal vagal nerves in the awake rat.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

J D Sinclair

Author Tools

Chat about Author

Papers

Restoration of hypoxic respiratory responses in the awake rat after carotid body denervation by sinus nerve section.

Respiratory effects of sectioning the carotid sinus glossopharyngeal and abdominal vagal nerves in the awake rat.