Adrenaline release evokes hyperpnoea and an increase in ventilatory CO₂ sensitivity during hypoglycaemia: a role for the carotid body

Abstract

Key pointsr Hypoglycaemia is counteracted by release of hormones and an increase in ventilation and CO 2 sensitivity to restore blood glucose levels and prevent a fall in blood pH.r The full counter-regulatory response and an appropriate increase in ventilation is dependent on carotid body stimulation.r We show that the hypoglycaemia-induced increase in ventilation and CO 2 sensitivity is abolished by preventing adrenaline release or blocking its receptors.r Physiological levels of adrenaline mimicked the effect of hypoglycaemia on ventilation and CO 2 sensitivity.r These results suggest that adrenaline, rather than low glucose, is an adequate stimulus for the carotid body-mediated changes in ventilation and CO 2 sensitivity during hypoglycaemia to prevent a serious acidosis in poorly controlled diabetes.Abstract Hypoglycaemia in vivo induces a counter-regulatory response that involves the release of hormones to restore blood glucose levels. Concomitantly, hypoglycaemia evokes a carotid body-mediated hyperpnoea that maintains arterial CO 2 levels and prevents respiratory acidosis in the face of increased metabolism. It is unclear whether the carotid body is directly stimulated by low glucose or by a counter-regulatory hormone such as adrenaline. Minute ventilation was recorded during infusion of insulin-induced hypoglycaemia (8-17 mIU kg −1 min −1 ) in Alfaxan-anaesthetised male Wistar rats. Hypoglycaemia significantly augmented minute ventilation (123 ± 4 to 143 ± 7 ml min −1 ) and CO 2 sensitivity (3.3 ± 0.3 to 4.4 ± 0.4 ml min −1 mmHg −1 ). These effects were abolished by either β-adrenoreceptor blockade with propranolol or adrenalectomy. In this hypermetabolic, hypoglycaemic state, propranolol stimulated a rise in P aCO 2 , suggestive of a ventilation-metabolism mismatch. Infusion of adrenaline (1 μg kg −1 min −1 ) increased minute ventilation (145 ± 4 to 173 ± 5 ml min −1 ) without altering P aCO 2 or pH and enhanced ventilatory CO 2 sensitivity (3.4 ± 0.4 to 5.1 ± 0.8 ml min −1 mmHg −1 ). These effects were attenuated by either resection of the carotid sinus nerve or propranolol. Physiological concentrations of adrenaline increased the CO 2 sensitivity of freshly dissociated carotid body type I cells in vitro. These findings suggest that adrenaline release can account for the ventilatory hyperpnoea observed during hypoglycaemia by an augmented carotid body and whole body ventilatory CO 2 sensitivity.

Adrenaline and the carotid body during hypoglycaemia: an amplifying mechanism?

“…Through intravenous adrenaline infusion, Thompson et al . () found that adrenaline mirrored the effects caused by hypoglycaemia, increasing both ventilation and CO 2 sensitivity. However, when adrenaline was infused after bilateral carotid sinus nerve section, the rise in minute ventilation was significantly attenuated and was found to be higher compared with control, denoting a clear ventilation–metabolism mismatch.…”

“…Another notable contribution of the study of Thompson et al . () is that their results point towards the existence of a bidirectional link between adrenaline and carotid body. It is well known, as eluded to above, that carotid body activation increases adrenaline release through the sympathoadrenal axis.…”

“…The recent study by Thompson et al . () further contributes to our understanding of the mechanisms involved in carotid body aberrant signalling since they showed that adrenaline can stimulate the carotid body during hypoglycaemia. It could be that adrenaline is a contributor to the hypertonicity and hyperreflexia generated by the carotid body in chronic conditions of hypertension and the metabolic syndrome.…”

“…In a recent study published in The Journal of Physiology , Thompson et al . () highlighted that the carotid body plays an important role in a counter‐regulatory response to hypoglycaemia. The authors showed that carotid body activation is crucial to match ventilation to the hypermetabolic state induced by hypoglycaemia, avoiding an increase in and consequently acidosis.…”

“…The data presented by Thompson et al . () bring new insights into the mechanisms by which the carotid body can participate in the regulation of metabolism. It is noteworthy to highlight the evidence of the important role of adrenaline in stimulating the carotid body‐mediated hyperventilation during hypoglycaemia.…”