NITRIC-OXIDE IN THE SENSORY FUNCTION OF THE CAROTID-BODY

Recent studies suggest that nitric oxide (NO) may act as a chemical me ssenger in the nervous system. Since neurotransmitters are considered necessary for the sensory function of the carotid body, and molecular 02 is a co-factor for NO synthesis, we examined whether (a) chemorecep tor tissue also synthesizes NO and if so, (b) does endogenous NO affec t chemosensory activity. Experiments were performed on carotid bodies obtained from anesthetized cats (n = 20). Distribution of nitric oxide synthase (NOS), an enzyme that catalyzes the formation of NO was exam ined using NADPH-diaphorase histochemistry. Many nerve plexuses innerv ating the chemoreceptor tissue were positive for NADPH-diaphorase, ind icating that the nerve fibers are the primary source of NO production in the carotid body. Radiometric analysis of NOS activity of the chemo receptor tissue averaged 1.94 pmol [H-3]citrulline/min/mg protein. NOS activity was significantly less in low pO2 reaction medium than in ro om air controls. Chemosensory activity in vitro increased in a dose-de pendent manner in response to L-omega-nitro arginine (L-NNA), an inhib itor of NOS activity. The effects of NOS inhibitor were enantiomer sel ective as evidenced by reversal of the responses by L- but not D-argin ine. These observations imply that endogenous NO is inhibitory to caro tid body sensory activity. cGMP levels Of L-NNA-treated carotid bodies were significantly less than untreated controls, suggesting that the actions of NO are coupled to the cGMP second messenger system, as else where in the nervous system. Based on the findings that (a) low pO2 de creased NOS activity and, (b) endogenous NO is inhibitory to the senso ry discharge, it is suggested that the mechanism(s) of sensory excitat ion by hypoxia in the carotid body may involve 'disinhibition' resulti ng from NO synthesis.