Nitric oxide mediated neural control of carotid body chemoreceptors

Nitric oxide (NO) has recently been shown to be a novel transmitter synthesized by specific neuronal populations. It plays important roles in diverse neural processes. The present study provides evidence for an additional site of action for NO, namely, the carotid body, an arterial chemoreceptor which senses blood PO2, PCO2 and pH, and reflexly influences cardiopulmonary function via primary afferent fibers in the carotid sinus nerve (CSN). The immunocytochemical study described in Part I of this dissertation demonstrates that the carotid body is innervated by an extensive plexus of nerve fibers that contain NO synthase. Denervation experiments indicate that these are mostly unmyelinated fibers originating from: (1) parasympathetic neurons located within the carotid body and along the CSN/glossopharyngeal nerve, which innervate blood vessels of the organ; and (2) sensory neurons in the petrosal ganglion whose axonal terminals closely associate with type I cells. The second part of the dissertation examined the action(s) of NO on chemoreceptors utilizing in vitro superfused and vascularly perfused preparations of the cat carotid body. It was observed that NO precursor inhibited, whereas NO synthase inhibitor enhanced hypoxia evoked chemoreceptor discharge. Moreover, the NO donor nitroglycerine inhibited the CSN discharge and stimulated cGMP formation in both blood vessels and type I cells. These findings indicate that NO is a inhibitory neuronal messenger in the carotid body that affects the process of chemoreception via its actions on the receptor elements and their associated blood vessels. The aims of Part III were to determine (1) whether centrifugal activity of CSN fibers provokes synthesis of NO in the carotid body, and (2) whether NO mediates the efferent neural control of the chemoreceptor. Experimental evidence was accumulated to support that NO could have two major functions within the carotid body. In addition to its potent actions on carotid blood vessels via traditional anterograde routes as one of the transmitters released by efferent autonomic fibers, NO released from nerve endings of sensory neurons may retrogradely interact with the presynaptic chemosensory type I cells. The former inhibits the steady-state CSN activity, and the later attenuates the dynamic chemoreceptor response to hypoxia. These cellular interactions constitute two morphologically distinct, but functionally complementary neuronal pathways mediating the efferent inhibitory control of carotid body chemoreceptors.