Glucocorticoids inhibit superoxide anion production and p22 phox mRNA expression in human aortic smooth muscle cells

Recent reports suggest that the increased production of reactive oxygen spe cies (ROS) in the vascular wall may contribute to the functional and struct ural changes associated with hypertension and atherosclerosis. Although glu cocorticoid therapy can promote atherosclerosis, protective effects of thes e compounds on vascular lesion formation have been reported. In the present study, we investigated whether ROS production in cultured human aortic smo oth muscle cells (HSMCs) can be modulated by glucocorticoids, Pretreatment of HSMCs with dexamethasone for 24 hours attenuated the basal and platelet- derived growth factor (PDGF)-AB- and angiotensin II-induced superoxide anio n (0(2)(.-)) production. PDGF-AB-stimulated O-2(.-) production was also inh ibited by prednisolone and hydrocortisone but not by other steroids, such a s testosterone and norgestrel. Incubation of HSMCs with glucocorticoids for 24 hours decreased 2',7'-dichlorodihydrofluorescein (DCHF) oxidation, an i ndicator of intracellular ROS levels. Dexamethasone decreased the mRNA expr ession of p22 phox, one of the components of NADPH oxidase, but had no effe ct on the activity of superoxide dismutase. The effects of dexamethasone on DCHF oxidation, and p22 phox mRNA expression and PDGF-AB-stimulated O-2(.- ) production were inhibited by the glucocorticoid receptor antagonist RU486 . These results indicate that glucocorticoids decrease O-2(.-) production b y HSMCs via a receptor-dependent pathway. This effect is likely to be media ted by a decrease in the generating system, such as downregulation of p22 p hox. mRNA, rather than an increased inactivation of O-2(.-). The inhibition of ROS production might contribute to the local protective effects that gl ucocorticoids have on vascular lesion formation.