Ischemic damage increases nitric oxide production via inducible nitric oxide synthase in the cochlea.
The present study was designed to elucidate the dynamic changes of nitric oxide (NO) production in the perilymph and to investigate the immunostaining for inducible nitric oxide synthase (iNOS) in the cochlea for 7 days after transient cochlear ischemia. Moreover, aminoguanidine, which is a selective iNOS inhibitor, was administrated immediately following ischemia and every 24h thereafter for 7 days to investigate whether the production of NO is dependent on the iNOS pathway. Significant increases in the oxidative NO metabolites, nitrite (NO(2)(-)) and nitrate (NO(3)(-)), were measured on day 1 using an in vivo microdialysis and on-line high performance liquid chromatography (HPLC) system. The immunostaining for iNOS was strongly expressed on days 1 and 4 and returned to normal on day 7 after the ischemia. The administration of aminoguanidine reduced the oxidative NO metabolites on day 1 and suppressed the expression of iNOS. These findings suggest that transient ischemia causes a remarkable increase in NO production in the perilymph, which might be attributable to the iNOS pathway.
Morizane
Isao
I
Department of Otolaryngology, Ehime University School of Medicine, Toon, Ehime 791-0295, Japan.
Hakuba
Nobuhiro
N
Hyodo
Jun
J
Shimizu
Yoshitaka
Y
Fujita
Kensuke
K
Yoshida
Tadashi
T
Gyo
Kiyofumi
K
D000818:Animals; D003051:Cochlea / Q000098:blood supply* / Q000378:metabolism*; D005849:Gerbillinae; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010498:Perilymph / Q000378:metabolism*; D015398:Signal Transduction
D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II