title: Impaired vasodilation and nitric oxide synthase activity in glucocorticoid-induced hypertension.
abstract: Synthetic glucocorticoids are among the most widely prescribed medications by physicians. Although they have a vast array of beneficial effects such as immunosuppression and anti-inflammation, excess glucocorticoids can lead to iatrogenic Cushing's syndrome, which includes hypertension and cardiovascular disease. The exact mechanism by which glucocorticoids elevate blood pressure is not completely understood, but it appears to be a complex pathology that involves increased responsiveness to vasoconstrictors and decreased vasodilator production. Nitric oxide is a vasodilator that plays a key role in blood pressure regulation, and previous studies have shown that a reduction in nitric oxide production or bioavailability contributes to hypertension. Tetrahydrobiopterin, a necessary cofactor for nitric oxide synthase activity, can affect nitric oxide production and bioavailability, with low levels causing decreased nitric oxide production. However, little is known about the interaction between glucocorticoids and tetrahydrobiopterin levels. In this review, the roles of nitric oxide and tetrahydrobiopterin in the pathogenesis of glucocorticoid hypertension will be discussed. Furthermore, the authors propose that glucocorticoids exert a genomic effect to decrease guanosine triphosphate cyclohydrolase I, the rate-limiting enzyme in the production of tetrahydrobiopterin. In the future, tetrahydrobiopterin supplementation in patients with iatrogenic Cushing's syndrome may prove to be beneficial and decrease mortality attributed to cardiovascular disease.
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology*; D003480:Cushing Syndrome / Q000139:chemically induced / Q000503:physiopathology; D004727:Endothelium / Q000166:cytology; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007049:Iatrogenic Disease; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D005938:Glucocorticoids; D001708:Biopterins; D019001:Nitric Oxide Synthase; C003402:sapropterin