Long-term use has been linked to sensorineural hearing loss and tinnitus through multiple pathways, including endothelial dysfunction with cochlear ischemia, which is mediated by reduced endothelial nitric oxide synthase (eNOS) activity and increased levels of asymmetric dimethylarginine (ADMA) [68,69,70,71,72,73]. This evidence concerns the gene NOS3 and sensorineural hearing loss disorder.