Saruta ( 25 ) has suggested that multiple factors are involved in glucocorticoid-induced hypertension in humans and animals: activation of the renin-angiotensin system due to an increase in plasma renin substrate, reduced activity of depressor systems, including the kallikrein-kinin system, prostaglandins, and the endothelium-derived relaxing factor nitric oxide, and increased pressor responses to angiotensin II and norepinephrine. This evidence concerns the gene KLK4 and hypertensive disorder.