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

Abstract

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 microg/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.

• Authors: Yi Zhang, Kevin D Croft, Trevor A Mori, Christopher G Schyvens, Katja U S McKenzie, Judith A Whitworth
• Journal: American journal of hypertension (Am J Hypertens) Vol. 17 Issue 3 Pg. 260-5 (Mar 2004) ISSN: 0895-7061 [Print] United States
• PMID: 15001201 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antioxidants
• Biomarkers
• Cyclic N-Oxides
• F2-Isoprostanes
• Glucocorticoids
• Spin Labels
• Sodium Chloride
• Dexamethasone
• tempol

Topics

• Animals
• Antioxidants (administration & dosage)
• Biomarkers (blood)
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Cyclic N-Oxides (administration & dosage)
• Dexamethasone (adverse effects)
• Disease Models, Animal
• Drug Therapy, Combination
• F2-Isoprostanes (blood)
• Glucocorticoids (adverse effects)
• Hypertension (chemically induced, prevention & control)
• Male
• Models, Cardiovascular
• Organ Size (drug effects)
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Sodium Chloride (administration & dosage)
• Spin Labels
• Systole (drug effects)
• Thymus Gland (drug effects)