Many forms of hypertension are associated with increased oxidative stress. This study investigated the effects of Tempol, a superoxide scavenger, on prevention and reversal of hypertension induced by the synthetic glucocorticoid dexamethasone (Dex) in the rat.Methods: Male Sprague-Dawley rats (n = 10 in each group) were treated with saline or Dex (10 g/kg/day subcutaneously) for 13 days. Tempol (1 mmol/L) was given in drinking water from 4 days before treatment (prevention) or from treatment day 8 (T8) (reversal). Systolic blood pressure (SBP) was measured by the tail-cuff method. Plasma F2-isoprostane concentrations were measured as a highly specific marker of oxidative stress. Thymus weight was measured as a marker of glucocorticoid activity.Results: Dex treatment increased SBP (122 5 to 136 3 mm Hg, P <.05) and plasma F2-isoprostane concentrations (P = .005). Tempol alone did not alter SBP, but Tempol pretreatment prevented Dex-induced hypertension compared with that in rats treated with Dex alone (128 4 and 144 7 mm Hg respectively, P' <.05). Tempol partially reversed Dex-induced hypertension (122 5 and 136 3 mm Hg, respectively, P' = .057). Thymus weight was decreased in Dex-treated rats compared with saline treated rats (157 10 saline and 105 6 mg/100 g body weight Dex, P <.0005). Tempol affect neither thymus weight nor F2-isoprostane concentrations.Conclusions: Chronic Dex treatment increased SBP and tended to increase oxidative stress shown as increased plasma F2-isoprostane concentrations. Tempol prevented and partially reversed Dex-induced hypertension, independent of improvement in systemic oxidative stress measured by F2-isoprostane concentrations.