It is mainly due to reduced production of endothelial nitric oxide synthase (eNOS)-derived NO [51,52,53]: many factors such as hypertension, angiotensin II and aging can modify transcriptional and post-transcriptional eNOS signaling, leading to loss of function of eNOS and consequently reduction in NO serum levels [51,52,53]. This evidence concerns the gene NOS3 and hypertensive disorder.