The antioxidant tempol prevents and partially reverses dexamethasone-induced hypertension in the rat

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. Male Sprague-Dawley rats ( n = 10 in each group) were treated with saline or Dex (10 μg/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 F 2-isoprostane concentrations were measured as a highly specific marker of oxidative stress. Thymus weight was measured as a marker of glucocorticoid activity. Dex treatment increased SBP (122 ± 5 to 136 ± 3 mm Hg, P < .05) and plasma F 2-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 F 2-isoprostane concentrations. Chronic Dex treatment increased SBP and tended to increase oxidative stress shown as increased plasma F 2-isoprostane concentrations. Tempol prevented and partially reversed Dex-induced hypertension, independent of improvement in systemic oxidative stress measured by F 2-isoprostane concentrations.