[Regulation of nitric oxide-cyclic guanosine monophosphate pathway on cochlear sensitivity].
OBJECTIVE
To investigate the effect of nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway on cochlear sensitivity. Methods Ten groups of guinea pigs were treated with the following solutions by whole cochlear perfusion for 2 hours: (1) Artificial perilymph; (2) L-arginine; 93) Ca(2+)-ATPase inhibitor; (4) Ca(2+)-ATPase inhibitor + L-arginine; (5) Ca(2+)-ATPase inhibitor + cGMP; (6) Ca 2+ ATPase inhibitor + L-arginine + Non-selective NOS inhibitor; (7) eNOS inhibitor; (8) eNOS inhibitor + Ca(2+)-ATPase inhibitor; (9) eNOS inhibitor + Ca(2+)-ATPase inhibitor + L-arginine; (10) eNOS inhibitor + Ca(2+)-ATPase inhibitor + L-arginine + nNOS inhibitor. The compound action potential (CAP) and cochlea microphonics (CM) were measured to assess the changes of cochlear sensitivity. After the perfusion, the cochleae were harvested and prepared for transmission electron microscopy.


RESULTS
The average threshold shift of CAP after perfusion Ca(2+)-ATPase inhibitor was 28.5 dB, and it was improved in group 4 with 9 dB by L-arginine, similar with group 5. The threshold shift of CAP in group 8 was 42.5 dB, and it decreased in group 9 by L-arginine, on this foundation nNOS inhibitor was added, increased threshold shift of CAP was 6.5 dB, similar with group 8. The results indicated that L-arginine could rivalry the role of Ca(2+)-ATPase inhibitor through the path of NO-cGMP. Transmission electron microscopy showed that Ca(2+)-ATPase inhibitor + L-arginine combined administration resulted in less vacuolization in out hair cell than that treated with Ca(2+)-ATPase inhibitor only.


CONCLUSIONS
The NO-cGMP pathway could regulate cochlear sensitivity; L-arginine may improve the function of Corti's organ via nNOS, and they indicate an important role of supporting cells in the modulation of cochlear function.
Li
Xing-Qi
XQ
Institute of Otorhinolaryngology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China. lixq@301hospital.com.cn
Jia
Xue-Bin
XB
Cao
Xiao-Ping
XP
Yu
Hong
H
Zhang
Ying
Y
D000200:Action Potentials; D000818:Animals; D003051:Cochlea / Q000378:metabolism / Q000502:physiology*; D003055:Cochlear Microphonic Potentials; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP