Pathophysiology of Chemoreception in Mammals

All mammals are critically dependent upon chemoreceptors for optimal cardiorespiratory regulation throughout the lifespan. Our knowledge of chemoreception and its importance in health and disease has increased exponentially over the past decade. The "extended" chemoreceptor pathway is now known to include not only the traditional inputs to medullary cardio-respiratory center neurons from peripheral and central chemoreceptors but also projections from carotid to central chemoreceptors as well as to hypothalamic neurons. Further, central chemoreceptors also serve as a site of convergence for several ascending and descending sensory inputs-accordingly inhibition/excitation of ( isolated) carotid chemoreceptors markedly influences central CO2 chemosensitivity in a hyperadditive fashion in the unanesthetized animal. Even during normal air-breathing normoxia in health , carotid chemoreceptors contribute highly significantly to the tonic, eupneic drive to breathe and to the increased sympathetically mediated vasoconstrictor activity in contracting muscle present during rhythmic exercise. Upregulation of chemosensitivity occurs in response to sustained and intermittent hypoxemia and to "stagnant" ( low blood flow) hypoxia. Maladaptive responses to this hyper-chemosensitivity include breathing instability and excessive sympathoexcitation leading to exacerbation of central and obstructive sleep apnea, heart failure and hypertension. Various means of modulating chemosensitivity has become a significant focus in devising treatments for these chronic diseases.