Nitric oxide in the sensory function of the carotid body

• Published in: Brain research Vol. 625; no. 1; pp. 16 - 22
• Main Authors: Prabhakar, Nanduri R., Kumar, Ganesh K., Chang Ho Chang, Agani, Faton H., Haxhiu, Musa A.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 15.10.1993; Amsterdam Elsevier; New York, NY
• Subjects: Amino Acid Oxidoreductases - antagonists & inhibitors; Amino Acid Oxidoreductases - metabolism; Animals; Arginine - analogs & derivatives; Arginine - pharmacology; Biological and medical sciences; Cardiorespiratory control. Arterial mecano- and chemoreceptor; Carotid body; Carotid Body - metabolism; Carotid Body - physiology; Cats; Chemoreceptor Cells - metabolism; Cyclic GMP - metabolism; Female; Fundamental and applied biological sciences. Psychology; Hypoxia; l-Nitro arginine; Male; NADPH Dehydrogenase - metabolism; NADPH-diaphorase; Nitric Oxide - metabolism; Nitric Oxide Synthase; Nitric oxidel Nitric oxide synthase; Nitroarginine; Oxygen - metabolism; Partial Pressure; Stereoisomerism; Tissue Distribution; Vertebrates: respiratory system; Nitric oxidel Nitric oxide synthase; Hypoxia; NADPH-diaphorase; Carotid body; l-Nitro arginine; Fissipedia; Carnivora; Vertebrata; Mammalia; Enzyme; Neuromediator; Cat; Nitrogen monoxide; Nitric oxide synthase; NADPH dehydrogenase; Chemoreceptor
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(93)90132-7

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 O 2 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 pO 2 reaction medium than in room air controls. Chemosensory activity in vitro increased in a dose-dependent manner in response to l-ω-nitro arginine ( l-NNA), an inhibitor of NOS activity. The effects of NOS inhibitor were enantiomer selective as evidence 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. Based on the findings that (a) low pO 2 decreased NOS activity and, (b) endogenous NO is inhibitory to the sensory discharge, it is suggested that the mechanism(s) of sensory excitation by hypoxia in the carotid body may involve ‘disinhibition’ inhibitory to the sensory discharge, it is suggested that the mechanism(s) of sensory excitation by hypoxia in the carotid body may involve ‘disinhibition’ resulting from NO synthesis.