Nitric oxide contributes to control of effusion in experimental otitis media.
OBJECTIVE
Nitric oxide (NO) is a small, short-lived free radical involved in cellular signaling and known to play a role in inflammation. It is generated on demand by the enzyme nitric oxide synthase (NOS) on arginine. We have previously found that mRNA encoding NOS is produced in the middle ear during otitis media. The role of NO was therefore explored in an experimental model of immune-mediated otitis media.


METHODS
Guinea pigs were systemically immunized and later challenged in the middle ear with the same antigen. One ear of each animal was challenged with antigen alone. In the opposite ear, antigen was combined with a potent inhibitor of NOS, N(G)-amino-L-arginine (L-NAA). After survival for 24, 48, or 72 hours, the middle ears were evaluated for otitis media.


RESULTS
Inhibition of NOS resulted in significantly increased middle ear effusion at all three time periods. This increase was blocked by the addition of excess 1-arginine, which bypasses the inhibitory effects of L-NAA. The infiltration of cells into the middle ear lumen and the hyperplasia of the middle ear mucosa were unaffected by L-NAA administration.


CONCLUSIONS
The results suggest that NO is involved in regulating the permeability of the middle ear vascular, the transudation of serum into the middle ear mucosa, and/or the movement of extracellular fluid across the middle ear mucosal epithelium.
Ryan
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Department of Surgery/Otolaryngology, UCSD School of Medicine and VA Medical Center, La Jolla, California 92093, USA. aryan@ucsd.edu
Bennett
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D000276:Adjuvants, Immunologic; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004432:Ear, Middle / Q000276:immunology / Q000473:pathology; D004790:Enzyme Induction / Q000502:physiology; D006168:Guinea Pigs; D006433:Hemocyanins / Q000276:immunology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010034:Otitis Media with Effusion / Q000276:immunology / Q000473:pathology*
D000276:Adjuvants, Immunologic; D009569:Nitric Oxide; D006433:Hemocyanins; D001120:Arginine; D019001:Nitric Oxide Synthase; C032808:keyhole-limpet hemocyanin