Tetrahydrobiopterin (BH4) acts as an important co-factor for endothelial ni
tric oxide synthase (eNOS). Glucocorticoids have been shown to inhibit expr
ession of the rate-limiting enzyme for tetrahydrobiopterin synthesis, GTP c
yclohydrolase, in other cell types. We hypothesized that endothelium-depend
ent vasodilator responses would be blunted in rats made hypertensive with d
examethasone. Further, we hypothesized that treatment of rat vascular segme
nts with dexamethasone would result in attenuation of endothelial function
accompanied by decreased GTP cyclohydrolase expression. We report that endo
thelium-dependent relaxation responses to the calcium ionophore A23187 are
reduced in aortic rings from dexamethasone-hypertensive rats compared with
sham values, Dexamethasone incubation abolishes contraction to N-omega-nitr
o-L-arginine (L-NNA, 10(-5)M) in endothelium-intact aortic rings, and inhib
its expression of GTP cyclohydrolase. We conclude that inhibition of BH4 sy
nthesis by glucocorticoid regulation of GTP cyclohydrolase expression may c
ontribute to reduced endothelium-dependent vasodilation characteristic of g
Iucocorticoid-induced hypertension.