Role of NO in the Carotid Body in Heart Failure

Increased levels of reactive oxygen species and angiotensin II with a concomitant decreased bioavailability of NO within the carotid body seem to play a pivotal role in the development of enhanced carotid body chemosensory activity in pacing-induced heart failure rabbits. A decrease of NO production in the carotid body contributes to an exaggerated carotid body chemoreceptor activity and carotid body function in heart failure rabbits. The two constitutive isomers of nitric oxide synthase (NOS), nNOS (or NOS-1) and eNOS (or NOS-3), are normally abundant in the carotid body as illustrated by western and immunohistochemical analysis of the carotid body. NOS inhibition enhances chemoreflex function in the normal condition, and both nNOS and eNOS expression in the carotid body is suppressed in heart failure. Overexpression of the nNOS gene in the carotid body elevates nNOS protein expression and NO production in heart failure animals to normal levels and reverses the enhanced chemoreceptor function in heart failure. Thus, a marked downregulation of endogenous NOS in the carotid body appears to play an important role in the enhanced peripheral chemoreflex in heart failure rabbits.