Role of neurotransmitter gases in the control of the carotid body in heart failure

The peripheral arterial chemoreflex, arising primarily from the carotid body in most species, plays an important role in the control of breathing and in autonomic control of cardiovascular function. The peripheral chemoreflex is enhanced in heart failure patients and animal models of heart failure and contributes to the sympathetic hyperactivity and breathing instability that exacerbates the progression of the disease. Studies in animal models have shown that carotid body chemoreceptor activity is enhanced under both normoxic and hypoxic conditions in heart failure due to disruption of local mediators that control carotid body function. This brief review highlights evidence that the alterations in the gasotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide in the carotid body contribute to the exaggerated carotid body function observed in heart failure.

► Gas transmitters NO, CO, and H2S modulate carotid body sensitivity and are altered in heart failure. ► Interactions among these gas pathways come together in the carotid body in heart failure to alter “chemosome” control of carotid body afferent activity. ► The totality of these interactions and the underlying physiological mechanisms that induce their change in heart failure remain to be more fully elucidated. ► These gas transmitter effects carry important clinical relevance given the importance of the carotid body in the genesis and maintenance of autonomic imbalance and breathing instability in heart failure.