Nitric oxide in the sensory function of the carotid body.
Recent studies suggest that nitric oxide (NO) may act as a chemical messenger in the nervous system. Since neurotransmitters are considered necessary for the sensory function of the carotid body, and molecular O2 is a co-factor for NO synthesis, we examined whether (a) chemoreceptor tissue also synthesizes NO and if so, (b) does endogenous NO affect 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 examined using NADPH-diaphorase histochemistry. Many nerve plexuses innervating the chemoreceptor tissue were positive for NADPH-diaphorase, indicating that the nerve fibers are the primary source of NO production in the carotid body. Radiometric analysis of NOS activity of the chemoreceptor tissue averaged 1.94 pmol [3H]citrulline/min/mg protein. NOS activity was significantly less in low pO2 reaction medium than in room air controls. Chemosensory activity in vitro increased in a dose-dependent manner in response to L-omega-nitro arginine (L-NNA), an inhibitor of NOS activity. The effects of NOS inhibitor were enantiomer selective as evidenced by reversal of the responses by L- but not D-arginine. These observations imply that endogenous NO is inhibitory to carotid 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 elsewhere in the nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
Prabhakar
N R
NR
Department of Physiology, Case Western Reserve University, Cleveland, OH 44106.
Kumar
G K
GK
Chang
C H
CH
Agani
F H
FH
Haxhiu
M A
MA
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002344:Carotid Body / Q000378:metabolism / Q000502:physiology*; D002415:Cats; D002628:Chemoreceptor Cells / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D013237:Stereoisomerism; D014018:Tissue Distribution
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase; D006152:Cyclic GMP; D010100:Oxygen