The nitric oxide system in glucocorticoid-induced hypertension

The blood pressure-raising effects of adrenocortical steroids with predominantly glucocorticoid activity, both naturally occurring and synthetic, are well known. Recent evidence suggests that the nitric oxide system plays a key role in the hypertension produced by glucocorticoids. Glucocorticoid actions at various sites in the nitric oxide synthase (NOS) pathway may result in elevated blood pressure. These include: alterations in l-arginine availability or transport; NOS2 and NOS3 downregulation; reduced cofactor bioavailability; NOS uncoupling; a concomitant elevation in reactive oxygen species and removal of nitric oxide (NO) from the vascular environment; alterations in whole body antioxidant status; and erythropoietin induced resistance to NO.