Sensory plasticity of the carotid body: Role of reactive oxygen species and physiological significance

Abstract

Recent studies have shown that acute intermittent hypoxia (IH) induces sensory plasticity of the carotid body manifested as sensory long-term facilitation (LTF), which requires prior conditioning with chronic IH and is mediated by reactive oxygen species (ROS). The purpose of this article is to provide a brief review of chronic IH-induced sensory LTF of the carotid body, sources of ROS, mechanisms underlying sensory LTF and its functional significance. Development of sensory LTF requires conditioning with several days of chronic IH. It is completely reversible following re-oxygenation, does not depend on the severity of hypoxia used for IH conditioning, not species specific and is selectively evoked by acute repetitive hypoxia but not by repetitive hypercapnia. Sensory LTF is not associated morphological changes in the carotid body and is expressed in chronic IH treated adult but not in neonatal rat carotid bodies. Chronic IH increases ROS levels in the carotid body involving 5-HT mediated activation of NADPH oxidase-2 (NOX2) and subsequent inhibition of the mitochondrial complex I. Sensory LTF can be prevented by inhibitors of 5-HT receptors, NOX inhibitors as well as by anti-oxidants. The signaling pathways mediating the sensory LTF are summarized in the second figure. It is suggested that sensory LTF contributes to the persistent sympathetic excitation under chronic IH.