Expression of inducible nitric oxide synthase (iNOS/NOS II) in the cochlea of 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 enzyme of NO, soluble guanylyl cyclase (sGC) in structures of the mammalian cochlea have been demonstrated. To date, no reports have been published regarding 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 factor alpha (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 specific antibodies to neuronal, endothelial and inducible NOS and to sGC. Initiated 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 of the organ of Corti, in the limbus, in nerve fibers and in a part of the perikarya of the spiral ganglion after LPS/TNFalpha-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 significant differences in both experimental groups. Endothelial eNOS and neuronal bNOS 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 sensory cells. Strong labeling for bNOS became evident in the endosteum of the cochlea, while in the endothelium of blood vessels and in the epithelium of the limbus only eNOS could be labeled. sGC could be detected in SL, in supporting and sensory cells of the organ of Corti, in nerve fibers, ganglion cells, 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 blood 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 ear.
Hess
A
A
Department of Oto-Rhino-Laryngology, University of Cologne, Joseph-Stelzmannstrasse 9, D-50924, Cologne, Germany.
Bloch
W
W
Huverstuhl
J
J
Su
J
J
Stennert
E
E
Addicks
K
K
Michel
O
O
D000818:Animals; D003051:Cochlea / Q000378:metabolism*; D004432:Ear, Middle / Q000187:drug effects*; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D006162:Guanylate Cyclase