Adrenaline activation of the carotid body: Key to CO 2 and pH homeostasis in hypoglycaemia and potential pathological implications in cardiovascular disease

Abstract Ventilatory and neuroendocrine counter-regulatory responses during hypoglycaemia are essential in order to maintain glycolysis and prevent rises in P a CO 2 leading to systemic acidosis. The mammalian carotid body has emerged as an important driver of hyperpnoea and glucoregulation in hypoglycaemia. However, the adequate stimulus for CB stimulation in hypoglycaemia has remained controversial for over a decade. The recent finding that adrenaline is a physiological activator of CB in hypoglycaemia raises the intriguing possibility that CB stimulation and hyperpnoea may be necessary to maintain pH in other adrenaline-related hypermetabolic states such as exercise. This review will therefore focus on 1) The important functional contribution of the CB in the counter-regulatory and ventilatory response to hypoglycaemia, 2) the proposed mechanisms that cause CB stimulation in hypoglycaemia including hormonal activation by adrenaline and direct low glucose sensing and 3) the possible pathological consequences of repetitive CB activation by adrenaline that could potentially be targeted to reduce CB-mediated cardiovascular disease.