An extensive plexus of nerve fibers capable of synthesizing nitric oxi
de was demonstrated in the cat carotid body by immunocytochemical and
biochemical studies of nitric oxide synthase. Denervation experiments
indicated that the axons originate from: (i) microganglial neurons loc
ated within the carotid body and along the glossopharyngeal and caroti
d sinus nerves, whose ramifications primarily innervate carotid body b
lood vessels; and (ii), sensory neurons in the petrosal ganglion, whos
e terminals end in association with lobules of type I cells. In the in
vitro superfused cat carotid body, the nitric oxide synthase substrat
e, L-arginine, induced a dose-dependent inhibition of carotid sinus ne
rve discharge evoked by hypoxia. In contrast, the nitric oxide synthas
e inhibitor, L-N-G-nitroarginine methylester, augmented the chemorecep
tor response to hypoxia, and this effect was markedly enhanced when th
e preparation was both perfused and superfused in vitro. The nitric ox
ide donor, nitroglycerine, inhibited carotid sinus nerve discharge, an
d immunocytochemistry revealed that this drug stimulated the formation
of cyclic 3', 5'-guanosine monophosphate in both type I cells and blo
od vessels. Our data indicate that nitric oxide is an inhibitory neuro
nal messenger in the carotid body, which affects the process of chemor
eceptor transduction/transmission via actions on both the receptor ele
ments and their associated blood vessels.