Birmingham Arterial Chemoreceptor and Hypoxia Group

Birmingham Arterial Chemoreceptor and Hypoxia Group Header version

Group Leaders: Professor Prem Kumar, Dr Andrew P Holmes, Dr Clare J Ray, Dr Andrew M Coney

Overview

Our research group focuses on defining the role of the carotid body chemoreceptors, in cardiovascular, respiratory and neuroendocrine physiology and pathology. We are interested in understanding how the carotid body senses oxygen, carbon dioxide, hypoglycaemia and other blood-borne chemicals. We also examine the mechanisms underlying the pathological changes in carotid body function that lead to neurogenic hypertension, cardiac arrhythmia and breathing instability associated with important diseases such as diabetes, obstructive sleep apnoea and COPD. We aim to develop new treatments to target the carotid body to improve cardiovascular function in these patients. 

Our research group

The sensing of arterial blood gases and other blood-borne chemicals is mediated via specialised chemoreceptor cells in the carotid body. Carotid body stimulation is important in initiating cardiovascular, respiratory and neuroendocrine reflexes in response to hypoxia, hypercapnia, hypoglycaemia and acidosis, and acts to preserve arterial blood gases, blood glucose and pH. However, in the certain diseases such as obstructive sleep apnoea, diabetes, COPD and heart failure the carotid body becomes over-active leading to neurogenic hypertension and arrhythmia, thereby increasing cardiovascular mortality in these patients.

Our research is aimed at (i) understanding the chemotransduction processes involved in these cells – from the molecular mechanisms involved in detecting the stimulus through to the initiation of afferent neural signals, (ii) characterising the mechanisms of carotid body over-activity in diseases including obstructive sleep apnoea, diabetes and COPD and iii) developing carotid body targeted drug treatments to reduce hypertension and arrhythmia.

We undertake in vivo measurements of cardiovascular, respiratory and neuroendocrine reflex function. In addition, we perform in vitro measurements of carotid body afferent neural discharge as well as detecting the localisation of cellular proteins with immunohistochemistry. The work is complemented by associated research with collaborators at Heartlands Hospital and the Queen Elizabeth Hospital, where human studies are performed to examine the impact of intermittent hypoxia/sleep apnoea and diabetes upon cardiorespiratory control. We also have strong national and international collaborations with researchers within the field and are active participants at major conferences.  

Current Projects

  • Evaluating the role of nitric oxide and mitochondria in carotid body O2 sensing
  • Examining the role of ecto-5’-nucleotidase (CD73) in establishing carotid body sensitivity to hypoxia and hypercapnia
  • Adrenaline activation of the carotid body: examining the importance of the carotid body in hypoglycaemia-induced hyperpnoea and the potential detrimental effects in cardiovascular disease
  • Investigating how co-morbidities of obstructive sleep apnoea and diabetes interact to worsen cardiovascular outcomes in patients
  • Exploring how early exposure (in utero or post-natal) to chronic intermittent hypoxia and inflammation impacts on carotid body development and if this predisposes to cardiovascular disease

Recent/ Selected Publications

  • Holmes AP, Ray CJ, Pearson SA, Coney AM & Kumar P (2018). Ecto-5’-nucleotidase (CD73) regulates peripheral chemoreceptor activity and cardiorespiratory responses to hypoxia. J Physiol (In Press) https://doi.org/10.1113/JP274498
  • Holmes AP, Ray CJ, Thompson EL, Alshehri Z, Coney AM & Kumar P (2018). Adrenaline activation of the carotid body: key to CO2 and pH homeostasis in hypoglycaemia and potential pathological implications in cardiovascular disease. Respir Physiol Neurobiol (In Press) DOI= 10.1016/j.resp.2018.05.008 
  • Holmes AP, Ray CJ, Coney AM & Kumar P (2018). Is carotid body physiological O2 sensitivity determined by a unique mitochondrial phenotype? Frontiers in Physiology 9:562 

    DOI=10.3389/fphys.2018.00562

  • Phillips TJ…Coney AM et al (2017). Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development. Nature Scientific Reports 7:9079 DOI:10.1038/s41598-017-06300-1
  • Thompson EL, Ray CJ, Holmes AP, Pye R, Wyatt CN, Coney AM & Kumar P (2016). Adrenaline release evokes hyperpnoea and an increase in ventilatory CO2 sensitivity during hypoglycaemia: a role for the carotid body. J Physiol 594(15):4439-52. 

Staff

PI(s)

Professor Prem Kumar

Dr Andrew P Holmes

Dr Clare J Ray

Dr Andrew M Coney

Students

Abdulaziz Alzahrani

Ziyad Alshehri 

Internal Collaborators

Dr Abd A Tahrani, Institute of Metabolism and Systems Research, NIHR Clinician Scientist, Honorary Consultant Endocrinologist at Heart of England NHS Foundation Trust

Dr Daniel A Tennant, Tennant Research Group, Institute of Metabolism and Systems Research

NHS Collaborators

Professor Brendan Cooper, Respiratory and sleep physiology, University Hospitals Birmingham NHS Foundation Trust

External Collaborators

Dr Keith J Buckler, University of Oxford, UK

Dr Christopher N Wyatt, Wright State University, USA