The antioxidant tempol prevents and partially reverses dexamethasone-induced hypertension in the rat.
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.
Zhang
Yi
Y
High Blood Pressure Research Unit, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
Croft
Kevin D
KD
Mori
Trevor A
TA
Schyvens
Christopher G
CG
McKenzie
Katja U S
KU
Whitworth
Judith A
JA
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000008:administration & dosage*; D003907:Dexamethasone / Q000009:adverse effects*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D028441:F2-Isoprostanes / Q000097:blood; D005938:Glucocorticoids / Q000009:adverse effects*; D006973:Hypertension / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D008955:Models, Cardiovascular; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage; D013113:Spin Labels; D013599:Systole / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects
D000975:Antioxidants; D015415:Biomarkers; D003497:Cyclic N-Oxides; D028441:F2-Isoprostanes; D005938:Glucocorticoids; D013113:Spin Labels; D012965:Sodium Chloride; D003907:Dexamethasone; C001803:tempol