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

被引:71
作者
Zhang, Y
Croft, KD
Mori, TA
Schyvens, CG
McKenzie, KUS
Whitworth, JA
机构
[1] Australian Natl Univ, John Curtin Sch Med Res, High Blood Pressure Res Unit, Canberra, ACT 2601, Australia
[2] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia
关键词
dexamethasone; hypertension; tempol; F-2-isoprostanes; oxidative stress;
D O I
10.1016/j.amjhyper.2003.11.004
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Background: 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 mug/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. Results: 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. Conclusions: 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. (C) 2004 American Journal of Hypertension, Ltd.
引用
收藏
页码:260 / 265
页数:6
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