Expression of inducible nitric oxide synthase (iNOS/NOS II) in the cochleaof guinea pigs after intratympanical endotoxin-treatment

Since NO is believed to be involved in cochlear physiology, presence of the constitutive isoforms of nitric oxide synthase (NOS), and the target enzym e of NO, soluble guanylyl cyclase (sGC) in structures of the mammalian coch lea have been demonstrated. To date, no reports have been published regardi ng the detection of the inducible isoform (NOS II) in the cochlea. In order to show the capability of iNOS expression in cochlear tissue, a mixture of proinflammatory bacterial lipopolysaccharides (LPS) and tumor necrosis fac tor a (TNF-alpha) was injected into the tympanic cavity of guinea pigs, vs. saline-solution as control. Paraffin sections of LPS/TNF-alpha treated and saline-treated cochleae (6 h) were examined immunohistochemically with spe cific antibodies to neuronal, endothelial and inducible NOS and to sGC. Ini tiated expression of iNOS in the cochlea was observed in the wall of blood vessels of the spiral ligament (SL) and the modiolus, in supporting cells o f the organ of Corti, in the limbus, in nerve fibers and in a part of the p erikarya of the spiral ganglion after LPS/TNF alpha-treatment. iNOS was not detected in saline-treated control tissue. Expression of both constitutive NOS-isoforms (endothelial and neuronal NOS) and of sGC showed no significa nt differences in both experimental groups. Endothelial eNOS and neuronal b NOS were detected co-localized in ganglion cells, in nerve fibers, in cells of the SL and in supporting cells of the organ of Corti, but not in sensor y cells. Strong labeling for bNOS became evident in the endosteum of the co chlea, while in the endothelium of blood vessels and in the epithelium of t he limbus only eNOS could be labeled, sGC could be detected in SL, in suppo rting and sensory cells of the organ of Corti, in nerve fibers, ganglion ce lls, in the wall of blood vessels and in the limbus-epithelium. While small amounts of NO, generated by bNOS and eNOS, seem to support the cochlear bl ood flow and auditory function as well. as neurotransmission, high amounts of iNOS-generated NO could have dysregulative and neurotoxic effects on the inner ear during bacterial and viral infections of the middle and inner ea r. (C) 1999 Elsevier Science B.V. All rights reserved.