Chronic intermittent hypoxia alters chemoreflex control of lumbar sympathetic nerve activity and carotid body protein expression

Abstract

In rats, exposure to chronic intermittent hypoxia (CIH) raises arterial pressure. CIH also increases carotid sinus nerve activity under normoxic conditions and results in an augmented response to hypoxia. The purpose of this study was to determine whether CIH augments chemoreflex control of lumbar sympathetic nerve activity (LSNA). In addition we measured expression of key regulatory proteins in the carotid bodies. Sprague Dawley rats were exposed to CIH. After 28 days, the rats were anesthetized, paralyzed, and mechanically ventilated. The lumbar sympathetic chain was exposed and the nerves were placed on bipolar platinum electrodes. We measured LSNA during six 20‐second apneas. In a separate group of rats, carotid bodies were removed, flash frozen, and later analyzed via Western blot for angiotensin type 1 receptor (AT1R) and neuronal nitric oxide synthase (nNOS) protein expression. Baseline LSNA and the LSNA response to 20‐sec apneas were higher in CIH rats vs. CON. Expression of AT1R protein was higher and nNOS protein lower in carotid bodies from CIH rats vs. CON. These results suggest that CIH results in augmented chemoreflex control of LSNA, and that this change in function is associated with changes in key regulatory proteins in the carotid body. These adaptations to CIH may be responsible in part for the arterial pressure elevations observed in this model. Funded by NIH #HL074072.