Effects Of Nitric Oxide And Atrial Natriuretic Peptide On Cochlear Blood Flow Of Guinea Pig

Objective: To provide some morphological basis for the interaction of atrial natriuretic peptide (ANP) and nitric oxide synthase (NOS) in cochlear regional blood, lymph flow and neuromodulation by studying their distribution and co-localization in guinea pig cochlear. To investigate the interactions between ANP and nitric oxide(NO)on cochlear blood flow (CoBF) of guinea pig, to search some new ways to prevent and heal the diseases related with cochlear microcirculation disorder.Methods: (1) Double indirect immunohistochemstry method was used to detect the locations of NOS and ANP in the normal cochlear tissue and cells. (2) Double indirect immunofluorescence was applied to investigate the co-location of NOS and ANP in the same cells of cochlear. (3) The guinea pigs were randomly allocated into five groups: ANP +L-Arginine (L-Arg) group, ANP +saline group, L-NG-Nitroarginine methyl ester (L-NAME) +ANP group, L-NAME +ANP +L-Arg group, and L-NAME +saline group. Otic capsule was exposed and a window was opened in scala tympani of the basal turn for drugs. CoBF was monitored continuously with laser Doppler flowmeter(LDF).Results: (1) Double positive staining of ANP and NOS was found in spiral modiolar artery (SMA), stria vascularis, spiral limbus, spiral ligaments, organ of Corti, and ganglion. However, No immunoactivity were found in the Reissner membrane and tectorial membrane. (2) Co-location of NOS and ANP can be seen in SMA cells, stria vascularis, spiral limbus, spiral ligaments, organ of Corti. Most of neurocytes were NOS and ANP double positive in ganglion, but some neurocytes were ANP positive only. (3) With the local application of ANP, the CoBF was increased significantly, and the CoBF got a further increase by adding the L-Arg. Local application of ANP could recover or partly recover the CoBF decrease caused by L-NAME. ANP was more powerful than L-Arg in this process, and L-Arg could further heighten the increases of CoBF by ANP. Saline could bring a weak CoBF recovery.Conclusion: The widely distribution of ANP and NO in the cochlea suggests that they may play important roles in the regulation of the CoBF flow, the endolymphytic balance and auditory signal transduction. The co-localization between ANP and NOS hints that they may play a coordinate role in the cochlear homeostasis. The CoBF could be heightened by ANP,L-Arg or both, which illustrates that NO and ANP play important roles in the CoBF self-regulation process.