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]. The gene discussed is NOS3; the disease is endothelial dysfunction.