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(Hypertension. 1998;32:1083-1088.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
Glucocorticoids Inhibit Superoxide Anion Production and p22 Phox mRNA Expression in Human Aortic Smooth Muscle Cells
From the Institut für Kardiovaskuläre Physiologie, Klinikum der Johann Wolfgang Goethe Universität Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Correspondence to Takeshi Marumo, MD, PhD, Institut für Kardiovaskuläre Physiologie, Klinikum der Johann Wolfgang Goethe Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. E-mail r.busse{at}em.uni-frankfurt.de
Abstract—Recent reports suggest that the increased production of reactive oxygen species (ROS) in the vascular wall may contribute to the functional and structural changes associated with hypertension and atherosclerosis. Although glucocorticoid therapy can promote atherosclerosis, protective effects of these compounds on vascular lesion formation have been reported. In the present study, we investigated whether ROS production in cultured human aortic smooth 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 anion (O2· -) production. PDGF-AB–stimulated O2· - production was also inhibited by prednisolone and hydrocortisone but not by other steroids, such as testosterone and norgestrel. Incubation of HSMCs with glucocorticoids for 24 hours decreased 2',7'-dichlorodihydrofluorescein (DCHF) oxidation, an indicator of intracellular ROS levels. Dexamethasone decreased the mRNA expression of p22 phox, one of the components of NADPH oxidase, but had no effect on the activity of superoxide dismutase. The effects of dexamethasone on DCHF oxidation, and p22 phox mRNA expression and PDGF-AB–stimulated O2· - production were inhibited by the glucocorticoid receptor antagonist RU486. These results indicate that glucocorticoids decrease O2· - production by HSMCs via a receptor-dependent pathway. This effect is likely to be mediated by a decrease in the generating system, such as downregulation of p22 phox mRNA, rather than an increased inactivation of O2· -. The inhibition of ROS production might contribute to the local protective effects that glucocorticoids have on vascular lesion formation.
Key Words: glucocorticoids • superoxide • free radicals • NADH • NADPH oxidase • muscle, smooth, vascular
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