 NO is produced in cells by a reaction mediated by the enzyme endothelial nitric oxide synthase eNOS. Experimental studies performed at Emory University have shown that tetrahydrobiopterin BH4, a naturally produced substance, is an essential factor for eNOS to be normally active, because in the event of BH4 deficiency, eNOS switches from producing NO to generating oxygen free radicals that increase oxidant stress in blood vessels leading to vascular damage. Moreover, studies have shown that administration of BH4 to animals with hypertension decreases blood pressure. 