These discrepancies highlight the multiple factors that regulate NO in vivo, including: the reduction in NO clearance in renal disease [11]; the elevation of naturally occurring NOS inhibitors in ADPKD (such as asymmetric dimethyl arginine) [51–53]; the genetic background of an individual [54]; and/or the need for functional stimulants to uncover the deficit [45]. This evidence concerns the gene NOS2 and autosomal dominant polycystic kidney disease.