As shown for oxidatively inactivated sGC, a highly specific eNOS activator or stimulator (not based on upregulation at the genetic or protein level) may fulfill a similar role for uncoupled/dysfunctional eNOS and only activate the damaged, oxidatively inactivated form of eNOS, which would represent a safe way to treat endothelial dysfunction without the risk of overdosing. The gene discussed is NOS3; the disease is endothelial dysfunction.